Publications by authors named "Michelly Cristiny Pereira"

30 Publications

  • Page 1 of 1

Genetic variants in are related to lower galectin-3 serum levels and clinical outcomes in systemic sclerosis patients: A case-control study.

Autoimmunity 2021 Jun 11;54(4):187-194. Epub 2021 May 11.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica - Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil.

Introduction: Systemic sclerosis (SSc) is a rare complex disease characterized by vascular damage, autoimmunity, and extensive skin and internal organs fibrosis. Galectin-3 (Gal-3) is encoded by gene (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) and it has been reported to play a central role in self-tolerance, inflammation, and fibrosis.

Objective: To investigate associations among single nucleotide polymorphisms (SNPs) and serum levels Gal-3 and SSc susceptibility and their clinical features.

Methods: A case-control study with 88 patients and 151 matched controls was performed. variants were analyzed by the TaqMan real-time polymerase chain reaction (PCR) system whereas Gal-3 serum levels were measured by sandwich enzyme linked immunosorbent assay (ELISA). Associations among genotypes, clinical features, and Gal-3 levels were performed by univariable and multivariable analysis through statistical packages.

Results: The rs4652 A/C genotype was more frequent in SSc patients than controls according to overdominant model [OR 1.89 (CI 95% 1.01 - 3.52);  = .046]. Also, rs4652 C/C polymorphic genotype was associated with lower patient Gal-3 levels ( = .03) and control group ( = 0.005), as noted by generalized linear model (GLM). The rs1009977 G/T controls showed higher Gal-3 levels than wild-type and polymorphic genotypes ( = .03); however, in SSc patients, no difference was found. None of the SNPs or Gal-3 levels was associated with clinical manifestations in SSc patients. Considering only the SSc group, GLM analysis pointed rs4652 and rs2075601, pulmonary arterial hypertension (PAH), myopathy, and health assessment questionnaire (HAQ) and scleroderma health assessment questionnaire (SHAQ) as important predictors for Gal-3 levels.

Conclusion: The rs4652 A/C was more frequent in SSc patients and related to lower Gal-3 levels. These findings were corroborated through a GLM to estimate Gal-3 values. Also, by model equations, Gal-3 levels may be predicted by HAQ, SHAQ, PAH, myopathy, and rs4652 and rs2075601 factors. In these ways, we suggest that galectins may be promising biomarkers to identify susceptibility to SSc as well as to identify HAQ, SHAQ, PAH, and myopathy outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08916934.2021.1919881DOI Listing
June 2021

Unveiling the pathogenesis of perineural invasion from the perspective of neuroactive molecules.

Biochem Pharmacol 2021 Jun 8;188:114547. Epub 2021 Apr 8.

Biochemistry Department, Federal University of Pernambuco, Recife, Brazil.

Perineural invasion (PNI) is characterized by an encounter between the cancer cells and neuronal fibers and holds an extremely poor prognosis for malignant tumors. The exact molecular mechanism behind PNI yet remains to be explored. However, it is worth-noting that an involvement of the neuroactive molecules plays a major part in this process. A complex signaling network comprising the interplay between immunological cascades and neurogenic molecules such as tumor-derived neurotrophins, neuromodulators, and growth factors constitutes an active microenvironment for PNI associated with malignancy. The present review aims at discussing the following points in relation to PNI: a) Communication between PNI and neuroplasticity mechanisms can explain the pathophysiology of poor, short and long-term outcomes in cancer patients; b) Neuroactive molecules can significantly alter the neurons and cancer cells so as to sustain PNI progression; c) Finally, careful manipulation of neurogenic pathways and/or their crosstalk with the immunological molecules implicated in PNI could provide a potential breakthrough in cancer therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2021.114547DOI Listing
June 2021

Immunopositivity for Siglec-15 in gastric cancer and its association with clinical and pathological parameters.

Eur J Histochem 2021 Mar 4;65(1). Epub 2021 Mar 4.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas - LINAT / Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino - NUPIT SG, Universidade Federal de Pernambuco, Recife.

The sialic acid-binding immunoglobulin-type lectin Siglec-15 is a promising target to cancer immunotherapy in several tumor types. The present study aimed to investigate Siglec-15 expression in gastric cancer (GC) patient tissue and to evaluate its clinical value. Siglec-15 expression was evaluated by immunohistochemistry with 71 patients. Siglec-15 staining was observed in tumor cells of 53 (74.64%) patients, with significant association with histologic classification and angiolymphatic invasion (p<0.05). Immunohistochemistry analysis also detected Siglec-15 in tumor-associated stroma cells (macrophages/myeloid cells). There was no significant association with outcomes parameters. Siglec-15 expression in well differentiated histological GC tissues and in the tumor microenvironment are potential targets to be further investigated as a novel prognostic factor for GC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/ejh.2021.3174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967265PMC
March 2021

Investigation of a new oxazolidine derivative in human resistance acute leukemia cells: deciphering its mechanism of action by label-free proteomic.

Naunyn Schmiedebergs Arch Pharmacol 2021 Jun 21;394(6):1153-1166. Epub 2021 Jan 21.

Research Center for Therapeutic Innovation (NUPIT-SG), Federal University of Pernambuco, Professor Moraes Rêgo s/n, Cidade Universitária, Recife, Pernambuco, 50670-901, Brazil.

The present study aimed to evaluate the mechanism of action of the antineoplastic activity of an oxazolidine derivative, LPSF/NB-3 (5-(4-cloro-benzilideno)-3-etil-2-tioxo-oxazolidin-4-ona). Cytotoxicity assays were performed in peripheral blood mononuclear cells (PBMCs) and resistant acute leukemia cell line (HL-60/MX1) by the MTT method. LPSF/NB-3 exhibited cytotoxicity in HL-60/MX1, but it was not toxic to healthy cells in the highest dose tested (100 μM). The protein extract of HL-60/MX1 cells treated with LPSF/NB-3 was subjected to proteomic analysis using two-dimensional chromatography coupled to mass spectrometry. We could identify a total of 2652 proteins, in which 633 were statistically modulated. Within the group of protein considered for the quantitative analysis with the established criteria, 262 were differentially expressed, 146 with increased expression and 116 with decreased expression in the sample treated with LPSF/NB-3 compared to the control. The following differentially expressed pathways were found: involving regulation of the cytoskeleton, DNA damage, and transduce cellular signals. Networks that were highlighted are related to the immune system. The ELISA technique was used to assess the immunomodulatory potential of LPSF/NB-3 in PBMCs. We observed significant decrease of IFNγ (p < 0.01) and dose-response pattern of the cytokines IL-6, IL-17A, IL-22, and IL-10. Therefore, results suggest that LPSF/NB-3 appears to modulate important pathways, including cell cycle and immune system regulatory pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00210-020-02024-8DOI Listing
June 2021

Increased serum levels of galectin-9 in patients with chikungunya fever.

Virus Res 2020 09 18;286:198062. Epub 2020 Jun 18.

Programa de Pós-Graduação em Inovação Terapêutica (PPGIT)/ UFPE, Brazil; Núcleo de Pesquisa em Inovação Terapêutica - Sueli Galdino (Nupit-SG), Brazil.

Chikungunya fever (CHIKF) is an arboviral disease that has caused an epidemic burst of chronic inflammatory joint disease in Latin America in the last few years. Efforts are being spent in understanding the mechanisms by which it may cause such articular damage and in determining possible biomarkers of the disease. Galectins (GAL) are a family of animal lectins with an affinity for beta-galactosides. They have multiple functions including working as receptors in innate immunity and as a control for inflammatory responses in both innate and adaptive immunity. They regulate functions of immune cells, such as lymphocytes and macrophages, which have a main role in the chikungunya inflammatory process. Galectins are also involved in chronification of viral diseases, participate in the immunopathogenesis of chronic joint diseases such as rheumatoid arthritis, and have a role in inflammation in other arboviral diseases, such as dengue. Thus, we intended to determine the serum levels of galectin-1, -3, -4, -7, and -9 in patients with subacute and chronic articular manifestations of CHIKF and to evaluate their associations with clinical manifestations. We evaluated 44 patients with clinical manifestations of CHIKF and serological confirmation with IgM and/or IgG chikungunya virus (CHIKV) antibodies. Forty-nine age- and gender-matched healthy individuals served as controls. Anti-CHIKV IgM and IgG antibodies and galectins serum levels were measured by ELISA. We found higher levels of GAL-9 (patients median 2192 [1500-2631] pg/mL, controls median 46.88 [46.88-46.88] pg/mL, p < 0.0001) and lower levels of GAL-3 (patients median 235.5 [175.5-351.8] pg/mL, controls median 2236.0 [1256.0-2236.0] pg/mL, p < 0.0001) in patients than in controls. There was no statistical difference in levels of GAL-1, -4 and -7 between patients and control groups. There was no difference in GAL-9 serum levels between patients with subacute or chronic symptoms (median 2148 [1500-2722] pg/mL x 2212 [1844-2500] pg/mL, p = 0.3626). A significant association of GAL-9 with joint stiffness, both in its duration and intensity, was found. These results may reflect the participation of GAL-9 in the immunopathogenesis of the inflammatory process in chikungunya fever, as morning stiffness may reflect the systemic inflammatory process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virusres.2020.198062DOI Listing
September 2020

Increased levels of the soluble oncostatin M receptor (sOSMR) and glycoprotein 130 (sgp130) in systemic sclerosis patients and associations with clinical parameters.

Immunobiology 2020 05 22;225(3):151964. Epub 2020 May 22.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Recife, PE, Brazil. Electronic address:

Objective: The objective of the present study was to evaluate the serum levels of soluble oncostatin M (OSM), OSM receptor (sOSMR) and glycoprotein130 (sgp130) in patients with systemic sclerosis (SSc), and the possible associations and correlations with clinical parameters.

Methods: Serum levels of OSM, sOSMR and sgp130 were evaluated by ELISA in eighty-four SSc patients and eighty-four healthy volunteers.

Results: SSc patients had significantly elevated levels of sOSMR and sgp130 when compared with healthy individuals (p < 0.0001 and p = 0.025, respectively). Diffuse cutaneous SSc and limited cutaneous SSc patients also presented higher levels of sOSMR when compared with healthy individuals (p = 0.003 and p = 0.0001, respectively). Patients with digital ulcers presented higher levels of sOSMR when compared to those without ulcers (p = 0.034). However, sOSMR levels were lower in patients with esophageal dysfunction than patients without this involvement (p = 0.038). OSM levels were undetectable in serum from SSc patients and healthy volunteers.

Conclusion: Serum levels of sOSMR and sgp130 are elevated in patients with systemic sclerosis. In addition, associations were observed with important clinical manifestations, suggesting that sOSMR is a candidate biomarker of this disease. More studies are needed to clarify the functions of IL-6 family cytokines in systemic sclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imbio.2020.151964DOI Listing
May 2020

Atorvastatin inhibits IL-17A, TNF, IL-6, and IL-10 in PBMC cultures from patients with severe rheumatoid arthritis.

Immunobiology 2020 05 30;225(3):151908. Epub 2020 Jan 30.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco (UFPE), Recife, PE, Brazil.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint damage, and it may present with comorbidities at the systemic level. The Th1/Th2/Th17 CD4 lymphocyte imbalance produces inflammatory cytokines, which begin to act, injuring joint tissue. Atorvastatin is a cholesterol- lowering drug with a range of biological effects including anti-inflammatory potential. Patients with rheumatoid arthritis who used statins exhibited clinical improvement. However, the mechanism is not fully understood. Therefore, we aimed to evaluate the RA immunomodulatory activity of atorvastatin.

Methods: Peripheral blood mononuclear cells (PBMCs) of RA patients and healthy donors were exposed to atorvastatin in different concentrations following a cytotoxicity assay. Th1, Th2, and Th17 cytokines profiles were evaluated in the culture supernatant by cytometric bead array (CBA). Data were analyzed using the Wilcoxon test, and differences were considered significant when p < 0.05.

Results: Atorvastatin showed no toxicity at the tested doses in RA PBMC cultures, and at 10μM, it showed the most significant results, reducing IL-17A (p = 0.002), TNF (p = 0.002), and IL-6 (p = 0.008) supernatant levels. The outcomes also revealed that only patients with more severe disease activity and those sensitive to corticoid treatments were responders to atorvastatin in vitro.

Conclusion: These findings suggest the potential immunomodulatory action of atorvastatin as a mechanism in rheumatoid arthritis treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imbio.2020.151908DOI Listing
May 2020

Galectin-9 gene (LGALS9) polymorphisms are associated with rheumatoid arthritis in Brazilian patients.

PLoS One 2019 10;14(10):e0223191. Epub 2019 Oct 10.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco (UFPE), Recife, Pernambuco, Brazil.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and hyperplasia, as well as cartilage and bone destruction. Several proteins are associated with the pathogenesis of the disease. Galectin-9 belongs to the family of lectins that are involved in various biological processes and have anti-inflammatory activity.

Objective: To investigate associations between the SNPs of the GAL-9 gene (LGALS9) and serum levels in rheumatoid arthritis patients. We extracted DNA from 356 subjects, 156 RA patients and 200 healthy controls from northeastern Brazil. Three polymorphisms (rs4795835, rs3763959, and rs4239242) in the LGALS9 gene were selected and genotyped using TaqMan SNP genotyping assay. Serum concentrations of galectin-9 were analyzed by ELISA.

Results: The rs4239242 TT genotype showed a positive association with RA (p = 0.0032, odds ratio = 0.28), and heterozygous TC were prevalent in the control group compared to RA patients (p = 0.0001, odds ratio = 7.99). Galectin-9 serum levels were significantly increased in RA patients compared to the control group (p<0.0001). Patients in remission had high levels of galectin compared to the moderate activity group (p<0.0001). Regarding the Clinical Disease Activity Index (CDAI), patients in remission or low activity presented high levels of galectin when compared to patients in severity (p<0.0001). Patients performing moderate activity had a significant value compared to patients who were in high disease severity (p = 0.0064). Interestingly, the AG genotype (rs3763959) has been associated with a higher presence of bone erosion in RA patients (p = 0.0436). The SNP rs4239242 TT genotype showed a positive association with RA in comparison to the control group. The AG genotype (rs3763959) has been associated with a higher presence of bone erosion in RA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223191PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786579PMC
March 2020

Galectin-1, -4, and -7 Were Associated with High Activity of Disease in Patients with Rheumatoid Arthritis.

Autoimmune Dis 2019 22;2019:3081621. Epub 2019 Jul 22.

Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco (UFPE), Recife, PE, Brazil.

Background: Due to the variety of functions that galectins (Gal) possess, it is clear that they participate in the pathogenesis of rheumatoid arthritis (RA). Although some studies demonstrate their functions, there is still no correlation with the clinical data of the disease, having the physiological meaning still unknown.

Objectives: To compare serum levels of Gal-1, -4, and -7 in patients with RA and healthy controls and to correlate them with clinical parameters.

Methods: Serum samples were collected from patients with RA and healthy donors to determine the serum levels of Gal-1, -4, and -7.

Results: Serum levels of Gal-1, -4, and -7 were significantly higher in RA patients compared to controls. We evaluated disease activity (CDAI) with serum levels of galectins and found that patients who were high in disease activity had high levels of galectin compared to the moderate activity group. Galectin-4 had higher levels in patients who were in high activity when compared to the group in remission or low activity. Evaluating the activity of the individual disease (DAS28), patients in high individual activity had high levels of Gal-4 when compared to the group in remission or low activity. We also found an association between positive rheumatoid factor and Gal-1 and Gal-4 levels.

Conclusion: Our results show for the first time the relationship between serum levels of galectin and the clinical parameters of patients with RA. Demonstrating their role in pathogenesis, new studies with galectins are needed to assess how they function as a biomarker in RA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/3081621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681614PMC
July 2019

CCL3, IL-7, IL-13 and IFNγ transcripts are increased in skin's biopsy of systemic sclerosis.

Exp Dermatol 2019 10 3;28(10):1172-1175. Epub 2019 Jul 3.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Recife, Brazil.

Although several cytokines and chemokines have been investigated as possible mediators of fibrosis in systemic sclerosis (SSc), specific correlation between cytokines and organ involvement have not been found yet, and a cytokine profile characteristic of SSc is far to be identified. We studied the profile of antifibrotic and profibrotic transcripts involved in skin of SSc patients. The mRNA expression was detected by fluorescence-based quantitative real-time PCR (qPCR) in skin's biopsies from 14 patients with SSc and 5 healthy controls. PDGF-A, CTGF, CCL3, IL-6, IL-13, IL-7, IFNγ, IL-17, IL-22 and RORc were analysed in these samples. CCL3, IL-7, IL-13 and IFN-γ were more expressed in skin's biopsy of patients with SSc (P = 0.0002, P = 0.0082, P = 0.0243, P = 0.0335, respectively) when compared with healthy controls. We also found a positive correlation between CCL3 and IL-7 transcripts (P = 0.0050 r = 0.7187). Furthermore, we observed that patients with lung involvement had lower expression of PDGF-A (P = 0.0385). We found an increase in IL-7, IFN-γ, CCL3 and IL-13 relative mRNA expressions on the skin's biopsy of patients with SSc, and a positive correlation between IL-7 and CCL3. These molecules are involved in the pathogenesis of SSc, and how their interactions occur should be the subject of further studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/exd.13982DOI Listing
October 2019

IL-27 in patients with Chikungunya fever: A possible chronicity biomarker?

Acta Trop 2019 Aug 7;196:48-51. Epub 2019 May 7.

Serviço de Reumatologia - Hospital das Clínicas da Universidade Federal de Pernambuco, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (Nupit-SG)/ UFPE, Endereço: Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife, PE, CEP: 50670-901, Brazil.

Background/purpose: Although many patients with chikungunya virus disease (CHIKVD), an arboviral disease characterized by sudden fever and incapacitating poliartralgia, develop chronic articular symptoms, the mechanisms involved in CHIKVD's chronification and its possible biomarkers remain poorly understood. Interleukin (IL)-17A, IL-21, IL-22, IL-29, and transforming growth factor (TGF)-β have been implicated in the pathogenesis of other inflammatory joint diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Since chronic manifestations of CHIKVD share many clinical and immunological characteristics with those diseases, we assessed the serum levels of those cytokines and analyzed their associations with clinical manifestations in patients with CHIKVD.

Methods: We evaluated 45 patients (36 female, mean age: 55.2 ± 13.8 years) with CHIKVD serologically confirmed by enzyme-linked immunosorbent assay (ELISA), articular manifestations upon evaluation, and no previous history of inflammatory rheumatologic diseases, along with 49 healthy age- and sex-matched controls. We tested anti-Chikungunya IgM and IgG antibodies and measured IL-17A, IL-21, IL-22, IL-27, IL-29, and TGF-β serum levels with specific ELISA kits.

Results: IL-27, IL-17A, and IL-29 appeared in most patients but not in controls. IL-27 serum levels were higher in patients with chronic symptoms (median: 523.0 pg/mL [62.5-1,048]) than in ones in the acute or subacute stage (median: 62.5 pg/mL [62.5-483.8], p = .008). In patients with CHIKVD, we found significant correlations between IL-27 levels and tender joint counts (r = .32, p = .006), along with associations between IL-17A levels and swollen joint counts (r = .315, p = .0352). Furthermore, patients with arthritis had higher IL-17A levels (median: 23.14 pg/mL [20.6-25.86]) than ones without (median: 20.29 pg/mL [3.91-22.43], p = .0352). We did not detect IL-22 in either group or IL-21 in patients with CHIKVD.

Conclusion: Serum levels of IL-17A, IL-27, and IL-29 were high in patients with CHIKVD and had important associations with articular manifestations, which might indicate the inflammatory nature of Chikungunya infection in patients with joint symptoms and the roles of those cytokines in the disease's pathophysiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actatropica.2019.05.005DOI Listing
August 2019

Dexamethasone inhibits cytokine production in PBMC from systemic sclerosis patients.

Inflammopharmacology 2019 Aug 8;27(4):723-730. Epub 2019 May 8.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica, Universidade Federal de Pernambuco, Avenida Professor Moraes Rêgo, 1235, Cidade Universitária, Recife, PE, 50670-901, Brazil.

Glucocorticoids (GC) are widely used in the treatment of SSc, although there is not much evidence to prove the benefits offered by these drugs in this disease. In this study, we evaluated the effects of a GC on cytokine production in peripheral blood mononuclear cells (PBMC) of SSc patients. The effect of dexamethasone (DEX) was evaluated in PBMC of 21 SSc patients and 10 healthy volunteers after stimulation of cells with anti-CD3 and anti-CD28. Cytokines IL-2, IL-4, IL-6, IL-10, IL-17A, IL-17F, IFN-γ, TNF, and IL-1β were quantified in the culture supernatant by CBA or ELISA. Of the patients evaluated in this study, 8 (38%) were taking corticosteroids, and esophageal dysfunction was more frequent in these patients when compared to those who did not take corticosteroids. DEX (1.000 nM) treatment in PBMC of SSc patients stimulated with anti-CD3 and anti-CD28 promoted a significant reduction in IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IL-1β (p < 0.001 for all), and IL-17F (p = 0.023) cytokines levels. We did not observe differences in response to in vitro treatment with DEX between groups of patients taking or not taking corticosteroids. In PBMC from healthy volunteers, we observed that DEX treatment significantly reduced IL-4, IFN-γ (p = 0.003 for both), IL-6, IL-10, IL-17A, and TNF (p = 0.002 for all) cytokines. These results show that DEX treatment in PBMC of SSc patients reduced the production of important cytokines involved in the pathogenesis of the disease, suggesting a possible mechanism of action of the CG in the treatment of SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10787-019-00600-wDOI Listing
August 2019

Potential Therapeutic Agents Against Par-4 Target for Cancer Treatment: Where Are We Going?

Curr Drug Targets 2019 ;20(6):635-654

Laboratory of Immunomodulation and New Therapeutical Approaches, Research Centre for Therapeutic Innovation Suely Galdino (NUPIT-SG), Federal University of Pernambuco, Recife, PE, Brazil.

One of the greatest challenges of cancer therapeutics nowadays is to find selective targets successfully. Prostate apoptosis response-4 (Par-4) is a selective tumor suppressor protein with an interesting therapeutic potential due to its specificity on inducing apoptosis in cancer cells. Par-4 activity and levels can be downregulated in several tumors and cancer cell types, indicating poor prognosis and treatment resistance. Efforts to increase Par-4 expression levels have been studied, including its use as a therapeutic protein by transfection with adenoviral vectors or plasmids. However, gene therapy is very complex and still presents many hurdles to be overcome. We decided to review molecules and drugs with the capacity to upregulate Par-4 and, thereby, be an alternative to reach this druggable target. In addition, Par-4 localization and function are reviewed in some cancers, clarifying how it can be used as a therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389450120666181126122440DOI Listing
July 2020

Correction to: Statins Inhibit Cytokines in a Dose-Dependent Response in Patients with Systemic Sclerosis.

Inflammation 2019 04;42(2):412

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas Suely Galdino, Universidade Federal de Pernambuco, Recife, Brazil.

One of the author's surname was incorrect. Anderson Ferreira de Almeida should be captured as Anderson Rodrigues de Almeida. The correct name is now presented above.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10753-018-0916-2DOI Listing
April 2019

Statins Inhibit Cytokines in a Dose-Dependent Response in Patients with Systemic Sclerosis.

Inflammation 2019 Apr;42(2):407-411

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas Suely Galdino, Universidade Federal de Pernambuco, Recife, Brazil.

Although statins have been successfully administered in the treatment of hypercholesterolemia and cardiovascular disease due to their lipid-lowering and anti-atherosclerotic action, they have shown immunomodulatory effects in several studies with immune-mediated diseases. The aim of this study was to investigate the effects of statins treatment on Th1, Th2, and Th17 cytokines production from stimulated peripheral blood mononuclear cells (PBMCs) obtained from Systemic Sclerosis (SSc) patients. We recruited 21 patients classified according to the American College of Rheumatology criteria for SSc for PBMCs culture analysis. Cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, IL-17A, and IL-17F) were quantified by ELISA or CBA, and patients were assessed for clinical and exam's variables. Simvastatin and atorvastatin at 50 μM promoted reduction in all cytokine levels with statistical significance, except for IL-6, which had its reduction only induced by the use of simvastatin. Statins, particularly simvastatin, appear to have an immunosuppressive effect in reducing all cytokine secretion levels from PBMCs of SSc in a dose-dependent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10753-018-0907-3DOI Listing
April 2019

Different profile of cytokine production in patients with systemic sclerosis and association with clinical manifestations.

Immunol Lett 2018 06 27;198:12-16. Epub 2018 Mar 27.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas - Núcleo de Pesquisa em Inovação Terapêutica (LINAT-NUPIT) - UFPE, Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, CEP: 50670-901, Brazil.

Immune dysregulation is a central process in the pathogenesis of systemic sclerosis (SSc). Cytokines produced by lymphocytes and monocytes are important mediators and induce tissue damage, recruit additional inflammatory cells, and promote extracellular matrix production and fibrosis. In the present research, we aimed to study the associations between levels of cytokines in serum and culture supernatants from peripheral blood mononuclear cells (PBMCs) and clinical manifestations in SSc patients. Serum samples were obtained from 56 SSc patients and 56 unrelated age- and gender-matched healthy individuals. Resting and anti-CD3/CD28-stimulated PBMC cultures were obtained from 19 SSc patients and 8 healthy controls. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF, and IFN-γ levels were measured by ELISA or CBA. Serum cytokines, except IL-17A, were below the kit detection limit in most of the patients and controls. In unstimulated PBMC, the production of TNF(p = 0.004), IL-10(p = .048), IL-2(p < 0.001), and IL-6 (p = 0.01) was higher in SSc patients than in healthy controls. After anti-CD3/CD28 stimulation, scleroderma PBMCs had lower concentrations of TNF(p = 0.009), IL-10(p = .018), and IL-2(p = .002) than HC. In unstimulated PBMC, IL-2 concentration was higher in patients with esophageal dysmotility (p = 0.04), and IL-10 levels had a positive correlation with modified Rodnan score (p = 0.03). After anti-CD3/CD28 stimulation, higher levels of IL-2 and IL-4 were observed in SSc patients with lung fibrosis (p = 0.01 and 0.006, respectively), and higher levels of IL-10 (p = 0.04) and IL-4 (p = 0.04) in patients with digital ulcers. In conclusion, SSc patients have a different profile of cytokine production and this was associated with clinical manifestations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2018.03.011DOI Listing
June 2018

Anticancer properties of thiophene derivatives in breast cancer MCF-7 cells.

Anticancer Drugs 2018 Feb;29(2):157-166

aLaboratory for Immunomodulation and New Therapeutic Approaches bLaboratory for Planning and Drug Synthesis, Federal University of Pernambuco (UFPE), Recife, Pernambuco cLaboratory Synthesis and Vectoring Molecules, Department of Biological Sciences, State University of Paraíba (UFPB), João Pessoa, Paraíba, Brazil.

Substitutions in thiophene structure give rise to new derivatives with different biological and pharmacological activities. The present study investigated the cytotoxicity activity of some thiophene derivatives in breast cancer cells maintained in two-dimensional (2D) or in three-dimensional (3D) culture and evaluated the anticancer mechanism of these compounds. Cytotoxicity assays were performed against untransformed cells and against breast cancer cell MCF-7. Apoptosis analysis and in-vitro migration assay were also performed to evaluate the mechanism of induction of cell death. All thiophene derivatives reduced the cell viability in breast cancer cells, showing cytotoxic activity (IC50<30 µmol/l), and SB-200 compound showed the best selectivity index in MCF-7 cells compared with doxorubicin in 2D culture. All thiophene derivatives significantly induced G0/G1 phase cell cycle arrest. However, only SB-83 treatment was effective against motility of MCF-7 cells in 2D culture (P=0.0059). The SB-200 derivative treatment induced an increased proportion of acridine orange/Hoechst double-stained cells (35.35 vs. 3.14%, P=0.0002) compared with nontreated cells, with apoptosis morphological alterations independent of caspase 7 activation (P>0.05). MCF-7 cells became less responsive to SB-200 and to doxorubicin in 3D culture compared with cells in 2D culture (higher IC50 values); however, SB-200 showed a better cytotoxic effect compared with doxorubicin in 3D culture. Therefore, the current study provides an insight into anticancer potential of thiophene derivatives, and further studies should be conducted to understand the mechanism by which thiophene derivatives act on cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CAD.0000000000000581DOI Listing
February 2018

Corticosteroid inhibits chemokines production in systemic sclerosis patients.

Steroids 2017 11 1;127:24-30. Epub 2017 Sep 1.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica (NUPIT), Universidade Federal de Pernambuco, Recife, PE, Brazil.

In this study, we evaluated glucocorticoids (GC) effects on cytokine/chemokine levels in serum samples and peripheral blood mononuclear cell (PBMC) production from systemic sclerosis (SSc) patients. We evaluated cytokine and chemokine levels in serum samples from SSc patients taking or not taking systemic glucocorticoids. PBMCs response to methylprednisolone (MP) was examined from 15 SSc patients and 8 healthy control subjects following PBMC stimulation with anti-CD3/CD28. Cytokine (IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10, and IL-17A) and chemokine (CXCL8/IL-8, CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) levels were quantified in serum and in PBMC culture supernatants by CBA or ELISA. Compared with patients not taking corticosteroids, we did not observe any significant differences in cytokines/chemokines serum levels in patients using systemic corticosteroids. After stimulation with anti-CD3/CD28, PBMCs treated with MP (100μM), showed a significant reduction of CCL2/MCP-1 (p=0.001), CCL5/RANTES (p=0.04), and CXCL8/IL-8 (p=0.003) levels in SSc patients. In PBMC from healthy controls, we observed decreased IFN-γ, TNF, IL-2, and IL-10 levels after MP treatment, compared with stimulated condition (p<0.01 for all). However in SSc patients, we did not find any significant reduction in these cytokine levels after MP treatment. In conclusion, CCL2/MCP-1, CCL5/RANTES, and CXCL8/IL-8 are chemokines that are potentially modulated by corticosteroids in vitro in SSc patients, but no effect was observed on IL-2, IL-4, IL-6, IL-10, IL-17A, TFN, and IFN-γ secretion. These results suggest a potential effect of GCs on SSc treatment and may reflect the benefit of their use in some patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2017.08.012DOI Listing
November 2017

Synthesis and in vitro anticancer activity of new 2-thioxo-oxazolidin-4-one derivatives.

Pharmacol Rep 2017 Aug 18;69(4):633-641. Epub 2017 Mar 18.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa para Inovação Terapêutica Suely Galdino (NUPIT-SG) - Federal University of Pernambuco (UFPE), Recife, Brazil; Laboratório de Planejamento e Síntese de Fármacos (LPSF), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG) - Federal University of Pernambuco (UFPE), Recife, Brazil. Electronic address:

Background: Oxazolidinones derivatives exhibit different biological properties, including anticancer activity. This work aimed to investigate the anticancer potential of five novel 2-Thioxo-oxazolidin-4-one derivatives.

Methods: Cytotoxicity assays were performed in human peripheral blood mononuclear cells (PBMCs) from healthy individuals and seven tumor cell lines. Apoptosis detection and cell cycle were evaluated by flow cytometry and the expression of genes involved in cell death processes by Real-Time PCR.

Results: All oxazolinedione derivatives were not cytotoxic in PBMCs. NB-5 showed the best results in cancer cells, inhibiting the growth of all tumor cell lines tested. NB-4 exhibited the highest cytotoxicity in Jurkat cells (IC=15.19μM) and NB-3 showed better anticancer effects in HL-60 (17.84μM). Only NB-4 significantly induced apoptosis in acute leukemia cells (p=0.001). All compounds caused a significant increase in expression of pro-apoptotic gene BID (p<0.05) and BECN1 (p<0.05). NB-3 significantly modulated the expression of RIPK3 (p=0.02) and DDIT3 (p=0.014), while NB-2 induced an increase of CDKN1A (p=0.03) and NB-4 induced PPARγ gene (p=0.0006).

Conclusion: NB-5 showed antitumor effects in solid and hematopoietic cancer cells, while other derivatives produced higher activity against hematopoietic cells. In acute leukemia cells, oxazolidinone derivatives modulated the expression of genes involved in apoptosis, ER stress, necroptosis and inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pharep.2017.03.005DOI Listing
August 2017

Increased IL17A, IFNG, and FOXP3 Transcripts in Moderate-Severe Psoriasis: A Major Influence Exerted by IL17A in Disease Severity.

Mediators Inflamm 2016 30;2016:4395276. Epub 2016 Nov 30.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil.

Psoriasis is a chronic and recurrent dermatitis, mediated by keratinocytes and T cells. Several proinflammatory cytokines contribute to formation and maintenance of psoriatic plaque. The Th1/Th17 pathways and some of IL-1 family members were involved in psoriasis pathogenesis and could contribute to disease activity. Therefore, we sought to analyse skin transcript levels of IL17A, IL22, RORC, IL8, IFNG, IL33, IL36A, FOXP3, and IL10 and correlate with clinic of patients with plaque-type psoriasis. In order to conduct that, we collected punch biopsies from lesional skin and obtained tissue RNA. After reverse transcription, qRT-PCR quantified the relative mRNA expression. The main results revealed increased transcripts levels of IL17A, IFNG, and FOXP3 in moderate-severe patients. Despite this, only IL17A can increase the chance to worsen disease severity. We also observed many significant positive correlations between each transcript. In conclusion, IL17A is elevated in lesional skin from psoriasis patients and plays crucial role in disease severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/4395276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155088PMC
August 2017

Reassessing the Role of the Active TGF-1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations.

Dis Markers 2016 14;2016:6064830. Epub 2016 Nov 14.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.

. To determine active TGF-1 (aTGF-1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients. . We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-1 by PBMC. The aTGF-1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. . TGF-1 serum levels were significantly higher in SSc patients than in HC ( < 0.0001). Patients with increased TGF-1 serum levels were more likely to have diffuse subset ( = 0.02), digital ulcers ( = 0.02), lung fibrosis ( < 0.0001), positive antitopoisomerase I ( = 0.03), and higher modified Rodnan score ( = 0.046). Most of our culture supernatant samples had undetectable levels of TGF-1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin. . Raised active TGF-1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/6064830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124685PMC
February 2017

Cytokine Profile in Gout: Inflammation Driven by IL-6 and IL-18?

Immunol Invest 2016 Jul 24;45(5):383-95. Epub 2016 May 24.

b Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Suely Galdino (NUPIT-SG), Centro de Ciências Biológicas, Universidade Federal de Pernambuco , Recife , Brazil.

Introduction: Gout is considered to be an autoinflammatory disease and the presence of monosodium urate (MSU) crystals stimulates activation of NPRL3 inflammasome and subsequently caspase-1, generating production of active IL-1β and IL-18. However, the association between serum cytokines levels and clinical manifestations of the disease is not yet well understood. We evaluated the serum profile of proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-22, and IL-23) and described their relationship with clinical and laboratory data.

Methodology: Thirty-nine male patients with gout (GG) were assessed for clinical and laboratory variables and cytokine levels were measured by ELISA. For the purposes of comparison, 34 males with no previous history of arthritis were also included in the study (CG).

Results: Seventeen participants (43%) exhibited active arthritis on evaluation. Levels of IL-18 were significantly higher in patients in relation to the CG (p = 0.0013). No statistically significant differences were found between the GG and CG for the other measured cytokines. There was a moderate correlation between IL-18 and ESR (R = 0.43, p = 0.0073), CRP (R = 0.47, p = 0.0025), and serum levels of IL-6 (R = 0.36, p = 0.023). An association was observed between serum levels of IL-6 and the presence of tophi (p = 0.005) and deformities (p = 0.0008), as well as a correlation between this cytokine and ESR (R = 0.41, p = 0.011) and CRP (R = 0.48, p = 0.02).

Conclusions: IL-18 is associated with inflammatory activity in gout, as well as with IL-6 levels, while IL-6 is associated with clinical and laboratory activity, the presence of tophi and articular deformities, and may be a prognostic marker of this pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/08820139.2016.1153651DOI Listing
July 2016

IL-17A, IL-22, IL-6, and IL-21 Serum Levels in Plaque-Type Psoriasis in Brazilian Patients.

Mediators Inflamm 2015 13;2015:819149. Epub 2015 Aug 13.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Centro de Ciências Biológicas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco (UFPE), Avenida Prof. Moraes Rego, 1235, Cidade Universitária, 50670-901 Recife, PE, Brazil.

Psoriasis is a chronic inflammatory skin disease characterized by alterations in cytokines produced by both Th1 and Th17 pathways. The aim of this study was to evaluate serum levels of pivotal cytokines and correlate them with clinical parameters. Serum samples from 53 psoriasis patients and 35 healthy volunteers, matched by the proportion of sex and age ratios, were collected for ELISA cytokine detection. Psoriasis Area and Severity Index (PASI) was assessed at the time of sampling in psoriasis patients. Our findings demonstrate that IL-17A, IL-22, and IL-6 serum concentrations were significantly higher in psoriasis patients than in the control group. No statistical correlation could be found between cytokines concentrations, PASI score, and age in this study. Although our results do not show any correlation between serum levels of IL-17A, IL-22, and IL-6 and disease activity, the present study confirms that they were increased in Brazilian psoriasis patients in comparison to healthy volunteers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/819149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550763PMC
June 2016

Evaluation of CD4(+)CD25(+)FoxP3(+) T cell populations, IL-10 production, and their correlation with clinical and biochemical parameters in sickle cell anemia patients with leg ulcers.

Cytokine 2015 Oct 22;75(2):310-5. Epub 2015 Jul 22.

Laboratory of Immunomodulation and Novel Therapeutic Approaches (LINAT), Research Center for Therapeutic Innovation (NUPIT), Universidade Federal de Pernambuco (UFPE), Recife 50670-901, Brazil. Electronic address:

Leg ulcers (LUs) are a debilitating complication of sickle cell anemia (SCA), with inflammation known to play a crucial role in their pathogenesis. Many studies have described the roles of T helper type 1 (Th1) and Th2 pathways in SCA; however, defects in anti-inflammatory responses are poorly understood. We evaluated interleukin (IL)-10 levels in serum and peripheral blood mononuclear cells (PBMCs) in SCA patients with leg ulcers (SCALU) and without leg ulcers (SCAWH) in addition to CD4(+) CD25(+)FoxP3(+) T cell populations and their its IL-10 expression. In stimulated and unstimulated PBMC cultures, SCALU patients produced higher levels of IL-10 than those in the SCAWH group. Higher levels of IL-10 in SCALU patients correlated with a history of osteonecrosis in stimulated and unstimulated cultures when compared with those in SCAWH. Immunophenotyping revealed that SCALU patients had a higher proportion of CD4(+)CD25(+)FoxP3(+), Tr1 and CD4(+)CD25(+)FoxP3(+)IL-10(+) T cells than other groups. Our findings revealed that IL-10 levels were increased in unstimulated cells from the SCALU group, and that this group also presented with a predominant CD4(+) CD25(+)FoxP3(+) cell population despite many of those cells being IL-10 negative.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2015.07.016DOI Listing
October 2015

Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement.

Clin Rheumatol 2015 Sep 11;34(9):1621-5. Epub 2015 Jul 11.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Recife, Brazil.

The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 ± 0.76 pg/ml) than in healthy individuals (1.89 ± 0.69 pg/ml; p < 0.0001). Patients with lung fibrosis had higher IL-35 levels than those without fibrosis (7.75 ± 1.36 and 3.08 ± 0.70 pg/ml, respectively, p = 0.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-015-3006-yDOI Listing
September 2015

The Role of PPAR Gamma in Systemic Sclerosis.

PPAR Res 2015 6;2015:124624. Epub 2015 May 6.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas da Universidade Federal de Pernambuco (LINAT-UFPE), 50670-901 Recife, PE, Brazil.

Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγ ligands have been studied in vitro and in vivo and some theories have emerged leading to new insights. Aberrant PPARγ function seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/124624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438188PMC
June 2015

Interferons and systemic sclerosis: correlation between interferon gamma and interferon-lambda 1 (IL-29).

Autoimmunity 2015 9;48(7):429-33. Epub 2015 Jun 9.

b Laboratório de Imunomodulação e Novas Abordagens Terapêuticas da UFPE , Brazil , and.

Background: Interferon (IFN)-λ1 is a newly described cytokine, member of type III interferons family, which is known for its antiviral, anti-proliferative and antitumor activity. Recent studies indicated that this cytokine has also immune-regulatory function, but its role in the pathogenesis of autoimmune diseases is not established yet. We evaluated serum levels of IFN-λ1 in systemic sclerosis (SSc) patients and healthy controls and its association with IFN-γ and clinical manifestations.

Methods: IFN-λ1 and IFN-γ serum levels were measured by ELISA from 52 patients with SSc and 53 healthy controls. Association of cytokines serum levels was sought with clinical parameters.

Results: IFN-λ1 and IFN-γ levels in SSc patients were significantly higher than those in healthy individuals (24.82 ± 8.78 and 11.04 ± 3.04 pg/ml, p < 0.0001; 34.11 ± 8.11 and 10.73 ± 2.77 pg/ml, p < 0.0001, respectively). We found a positive correlation between IFN-λ1 and IFN-γ levels in SSc patients (p = 0.0103, r = 0.3526). IFN-γ levels were associated with muscle involvement (p = 0.0483).

Conclusion: We first showed raised IFN-λ1 levels in SSc patients. Furthermore, we found a correlation between IFN-λ1 and IFN-γ levels and an association between IFN-γ and myositis. Additional in vitro and in vivo studies are needed to understand IFN-λ1 role in SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/08916934.2015.1054028DOI Listing
August 2016

Simvastatin inhibits cytokines in a dose response in patients with rheumatoid arthritis.

Inflamm Res 2014 Apr 14;63(4):309-15. Epub 2014 Jan 14.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, Brazil.

Objective And Design: To evaluate the effects of simvastatin in peripheral blood mononuclear cell (PBMC) cytokines profiles and correlate with the disease state of rheumatoid arthritis (RA) patients.

Methods: The PBMC from 22 RA patients were purified and stimulated or not stimulated with phorbol myristate acetate/ionomycin and were treated with simvastatin in different doses. Cytokine levels were quantified by ELISA and patients were assessed for clinical and laboratory variables. This assessment included disease activity measures [Clinical Disease Activity Index (CDAI), Disease Activity Score for 28 joints (DAS28)] and a Health Assessment Questionnaire.

Results: The IL-17A, IL-6, IL-22 and IFN-γ were significantly reduced in a dose response after simvastatin treatment (50 μM, p = 0.0005; p < 0.0001; p < 0.02; p = 0.0005, respectively). The IL-17A and IL-6 cytokines were also significantly reduced in lower concentrations of simvastatin (10 μM) compared to controls (p = 0.018; p = 0.04) and compared to the standard drug (p = 0.007; p = 0.0001). The results also showed that only RA patients with severe disease (DAS28 >5.1 and CDAI >22) had poor response to simvastatin in reducing cytokines levels, mainly for IL-17A and IL-22 cytokines (p = 0.03; p = 0.039, respectively).

Conclusion: The RA patients in clinical remission, mild or moderate had lower levels of all cytokines analyzed after simvastatin treatment, showing that these patients have better response to treatment. Our findings suggest that the simvastatin therapy modulates different cytokines in a dose dependent manner and its effect is associated with stratification of patients according to disease activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00011-013-0702-4DOI Listing
April 2014

Evaluation of Th17 related cytokines associated with clinical and laboratorial parameters in sickle cell anemia patients with leg ulcers.

Cytokine 2014 Feb 25;65(2):143-7. Epub 2013 Dec 25.

Laboratory of Immunomodulation and Novel Therapeutic Approaches (LINAT), Research Center for Therapeutic Innovation (NUPIT), UFPE, Recife, Brazil. Electronic address:

Leg ulcers (LUs) represent one of the main causes of morbidity in sickle cell anemia (SCA). This manifestation has been related to hemolysis, infections predisposition and inflammation that leads cytokines secretion. In this context, our study aimed to evaluate Th17 related cytokines (IL-6, IL-17A, IL-22 and IL-23) in serum and peripheral mononuclear cells culture supernatants with and without lymphoproliferative stimulation (anti-human CD3 and anti-human CD28). The cytokines levels were also correlated to clinical, hematological and biochemical parameters in SCA patients with and without LUs history (SCALU and SCAWH) as well as in healthy controls. In SCALU patients, high levels of IL-17A were associated with absence of acute chest syndrome (ACS, p=0.0328). The other clinical parameters analyzed (osteonecrosis, stroke, priapism, splenectomy and blood transfusions history) were not significantly related with other cytokine levels. In SCALU patients was also observed that IL-17A increased levels were associated with high levels of LDH (p=0.0130), the same association pattern was found for IL-6 (0.0160) and IL-22 (p=0.0165) in the SCALU group. Interestingly, we did not find statistical correlations with these parameters in SCAWH group. The other hematological parameters (hemoglobin, leucocyte and reticulocyte count) and indirect bilirrubin did not show any correlation with analyzed cytokines in both groups. So, for the first time, we show that IL-17A present in SCALU patients may exert a preventive role in the ACS development. Furthermore, IL-6, IL-17A and IL-22 accompanied the LDH levels only in SCALU patients suggesting to serve as additional markers of hemolysis or to be related with immunity response against extracellular pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2013.11.012DOI Listing
February 2014

Synthesis of a novel thiazolidinedione and evaluation of its modulatory effect on IFN- γ , IL-6, IL-17A, and IL-22 production in PBMCs from rheumatoid arthritis patients.

Biomed Res Int 2013 1;2013:926060. Epub 2013 Sep 1.

Serviço de Reumatologia do Hospital das Clínicas (HC), Universidade Federal de Pernambuco (UFPE), Rua Tereza Amélia, s/n, Cidade Universitária, 50670-901 Recife, PE, Brazil ; Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino (NUPIT-SG), Universidade Federal de Pernanbuco, (UFPE), Rua Tereza Amélia, s/n, Cidade Universitária, 50670-901 Recife, PE, Brazil.

Rheumatoid arthritis (RA) is an autoimmune disease frequently characterized by chronic synovitis of multiple joints. The pathogenesis of RA is complex and involves many proinflammatory cytokines as Th17 related ones. PPAR γ is a nuclear receptor activator that represses proinflammatory gene expression. Thus, this work aimed to synthetize a new thiazolidinedione (TZD) analogue based on a well-known anti-inflammatory and PPAR γ agonist activity of this ring and evaluate its anti-inflammatory activity. After chemical structure confirmation, the compound named 5-(5-bromo-2-methoxy-benzylidene)-3-(2-nitro-benzyl)-thiazolidine-2,4-dione TM17 was submitted to cytokine releasing inhibition and PPAR γ genetic modulation assays. The new compound showed no toxicity on human and murine cells, decreasing IL-6 secretion by murine splenocytes and reducing IL-17A, IL-22, and IFN- γ expression in peripheral blood mononuclear cells from patients with RA. TM17 was more efficient in modulating the mRNA expression of PPAR γ than its well-used TZD agonist rosiglitazone. Surprisingly, TM17 was efficient on IL-17A and IFN- γ reduction, like the positive control methylprednisolone, and presented a better effect on IL-22 levels. In conclusion, PBMCs obtained from RA patients under TM17 treatment present a significant reduction in IL-17A, IL-22, and IFN- γ levels, but not IL-6 when compared with nontreated cells, as well as increase PPAR γ mRNA expression in absence of stimulus addressing it as a promising molecule in RA treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2013/926060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773918PMC
April 2014