Publications by authors named "Trinidad García-Iglesias"

22 Publications

  • Page 1 of 1

Cytokines (IL-15, IL-21, and IFN-γ) in rheumatoid arthritis: association with positivity to autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) and clinical activity.

Clin Rheumatol 2019 Nov 17;38(11):3061-3071. Epub 2019 Jul 17.

Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, No. 950, 44340, Guadalajara, Jalisco, Mexico.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity.

Methodology: This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI).

Results: The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices.

Conclusions: Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points • IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. • RF, anti-CCP, and anti-MCV had higher levels in early than established RA. • IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. • Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-019-04681-4DOI Listing
November 2019

Toxicity of silver nanoparticles in mouse bone marrow-derived dendritic cells: Implications for phenotype.

J Immunotoxicol 2019 12 2;16(1):54-62. Epub 2019 Apr 2.

Department of Physical Chemistry, Center of Nanoscience and Nanotechnology, Ensenada B.C., Mexico.

Silver nanoparticles (AgNP) are one of the most studied nanoparticles due to their anti-bacterial, -fungal, -viral, -parasitic, and -inflammatory properties. This raises the need to evaluate the toxicity and biological effects of AgNP in the immune system in order to develop new safer biomedical products. In this study, an AgNP formulation currently approved for veterinary applications was applied to mouse bone marrow-derived dendritic cells (BMDC), considered important antigen-presenting cells of the immune system, to evaluate cytotoxicity, genotoxicity, and any significant influence on expression of cellular markers associated with BMDC phenotype and maturation status. The results showed that after 12 h of AgNP exposure, a significant decrease in BMDC viability occurred at the highest concentration tested (1.0 µg AgNP/ml) and at lower doses, the cells maintained membrane integrity and metabolic activity. DNA damage was not significant with any AgNP level aside from the 1.0 µg AgNP/ml level. Regarding phenotype, no differences in expression of CD40 (co-stimulatory molecule highly present in mature BMDC) or in CD273 (a marker for inhibitory T-cell response) were observed. The current results showed that the toxicity of this AgNP formulation was dose-related. The findings also suggest BMDC could maintain structural conservation of co-stimulatory/co-inhibitory surface molecules after 12 h of exposure to this AgNP. This work represents the first step in identifying the toxic effects of this AgNP formulation on dendritic cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1547691X.2019.1584652DOI Listing
December 2019

Macrophage Migration Inhibitory Factor Levels in Gingival Crevicular Fluid, Saliva, and Serum of Chronic Periodontitis Patients.

Biomed Res Int 2019 5;2019:7850392. Epub 2019 Feb 5.

Instituto de Investigación en Odontología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p<0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p<0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/7850392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379857PMC
June 2019

Th1/Th17 Cytokine Profile is Induced by Macrophage Migration Inhibitory Factor in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients.

Curr Mol Med 2018 ;18(10):679-688

Instituto de Investigacion en Ciencias Biomedicas, CUCS, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Background: Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that plays a crucial role as a regulator of the innate and adaptive immune responses and takes part in the destructive process of the joint in rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-17A, and IL- 17F in peripheral blood mononuclear cells (PBMC) from RA patients and control subjects (CS).

Methods: The PBMC from RA patients and CS were stimulated for 24 hours with combinations of LPS, rhMIF or the MIF antagonist ISO-1. Cytokine profiles were measured using a multiplex immunoassay and, macrophage migration inhibitory factor (MIF) was determined by ELISA kit.

Results: The PBMC of CS and RA produced Th1 and Th17 cytokines under stimulation with rhMIF, however, this effect was higher in the cells of RA patients. The rhMIFstimulated PBMC from RA patients produced higher levels of Th1 and Th17 cytokines in comparison with unstimulated cells: TNF-α (538.81 vs. 5.02 pg/mL, p<0.001), IFN-γ (721.90 vs. 8.40 pg/mL, p<0.001), IL-1β (150.14 vs. 5.17 pg/mL, p<0.05), IL-6 (19769.70 vs. 119.85 pg/mL, p<0.001), IL-17A (34.97 vs. 0.90 pg/mL, p<0.01) and IL-17F (158.43 vs. 0.92 pg/mL, p<0.001).

Conclusion: These results highlight the potential role of MIF in the establishment of the chronic inflammatory process in RA via Th1 and Th17 cytokine profile induction and provide new evidence of the role of MIF to stimulate the IL-17A and IL-17F expression in PBMC from RA and CS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1566524019666190129123240DOI Listing
October 2019

Adhesion, proliferation, and apoptosis in different molecular portraits of breast cancer treated with silver nanoparticles and its pathway-network analysis.

Int J Nanomedicine 2018 22;13:1081-1095. Epub 2018 Feb 22.

Laboratory of Immunology and Institute of Experimental and Clinical Therapeutics, Department of Physiology, University Center of Health Sciences, University of Guadalajara, Jalisco, Mexico.

Background: Silver nanoparticles (AgNPs) have attracted considerable attention due to the variety of their applications in medicine and other sciences. AgNPs have been used in vitro for treatment of various diseases, such as hepatitis B and herpes simplex infections as well as colon, cervical, and lung cancers. In this study, we assessed the effect on proliferation, adhesion, and apoptosis in breast cancer cell lines of different molecular profiles (MCF7, HCC1954, and HCC70) exposed to AgNPs (2-9 nm).

Methods: Breast cancer cell lines were incubated in vitro; MTT assay was used to assess proliferation. Adhesion was determined by real-time analysis with the xCELLingence system. Propidium iodide and fluorescein isothiocyanate-Annexin V assay were used to measure apoptosis. The transcriptome was assessed by gene expression microarray and Probabilistic Graphical Model (PGM) analyses.

Results: The results showed a decreased adhesion in breast cancer cell lines and the control exposed to AgNPs was noted in 24 hours (≤0.05). We observed a significant reduction in the proliferation of MCF7 and HCC70, but not in HCC1954. Apoptotic activity was seen in all cell lines exposed to AgNPs, with an apoptosis percentage of more than 60% in cancer cell lines and less than 60% in the control. PGM analysis confirmed, to some extent, the effects of AgNPs primarily on adhesion by changes in the extracellular matrix.

Conclusion: Exposure to AgNPs causes an antiproliferative, apoptotic, and anti-adhesive effect in breast cancer cell lines cultured in vitro. More research is needed to evaluate the potential use of AgNPs to treat different molecular profiles of breast cancer in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S152237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826086PMC
April 2018

MIF promotes a differential Th1/Th2/Th17 inflammatory response in human primary cell cultures: Predominance of Th17 cytokine profile in PBMC from healthy subjects and increase of IL-6 and TNF-α in PBMC from active SLE patients.

Cell Immunol 2018 02 26;324:42-49. Epub 2017 Dec 26.

Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico. Electronic address:

Macrophage migration Inhibitory Factor (MIF) is a cytokine associated with the pathogenesis of autoimmune inflammatory diseases. There is evidence that MIF functions in a positive-feedback-loop with proinflammatory cytokines and could perpetuate the inflammatory process in Systemic Lupus Erythematosus (SLE).The aim of this study was to assess the effect of recombinant-human-MIF (rhMIF) on the expression of Th1, Th2 and Th17 cytokines in Peripheral Blood Mononuclear Cells (PBMC) from Healthy Subjects (HS) and SLE patients. The PBMC were isolated from SLE patients classified according to the 1997 SLE ACR criteria and HS donors; all subjects included were women from an unrelated Mexican-Mestizo population. The PBMC isolated were stimulated with rhMIF, LPS and ISO-1 in different combinations; Th1, Th2 and Th17cytokine profiles levels were determined by MAGPIX Bio-plex assay in supernatants from cell cultures. We observed in supernatants of PBMCs from HS treated with rhMIF a predominance of Th17 cytokine profile with an increase of IL-17A, IL-17F and IL-21 versus PBMCs from SLE patients, which showed an inflammatory profile represented by increase of IL-6 cytokine. According to SLE remission/activity presented at enrollment in the study (Mex-SLEDAI index), the PBMC from active SLE patients showed higher levels of TNF-α and IL-6 versus PBMC from remission SLE patients. In conclusion, our results suggest that MIF can induce a differential inflammatory response in physiological and pathological conditions with a predominance of a Th17 cytokine profile in PBMC from HS and an increase in TNF-α and IL-6 expression in PBMC from active SLE patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellimm.2017.12.010DOI Listing
February 2018

Combination effect naringin and pravastatin in lipid profile and glucose in obese rats.

Life Sci 2018 Jan 2;193:87-92. Epub 2017 Dec 2.

Laboratory Pharmaceutical Research and Development, Department of Pharmacobiology, Exact Sciences and Engineering Center, University of Guadalajara, Marcelino García Barragan Blvd. 1421 P.C. 44430, Guadalajara, Jal 01 33 13785900, Mexico. Electronic address:

Aims: The purpose of this study was to compare the effect of naringin 100mg/kg in combination with pravastatin 10mg/kg by gavage for 6weeks compared with monotherapy over lipid profiles, glucose levels and weight in murine model of obesity.

Main Methods: The study design was planned with 5 groups of 6 male Wistar Albina rats: Group 1: control with balanced food and vehicle (C-); Group 2: control with Obesity and vehicle (C+); Group 3: Obesity+naringin (N); Group 4: Obesity+pravastatin (P); Group 5: Obesity+pravastatin+naringin (NP). Obesity was developed with a food model.

Key Findings: The naringin groups showed a decrease in weight gain and low glucose values compared to the control group (weight NP:311.4 vs C+:348.6; glucose NP: 173.12 vs C+:235.56) (p<0.05); the group with naringin+pravastatin combination showed the total cholesterol (TC), LDL and triglycerides (TGs) to normal levels (TC NP:51.6 vs C+:83.4; LDL NP:9.32 vs C+:32.32; TGs NP:39.4 vs C+:89.4) (p<0.05); but was not statistically significant compared with monotherapy.

Significance: The combination of naringin and pravastatin did not appear to be better than monotherapy on lipids, but its use could generate euglycemic and antiobesogenic effects, in addition to diminishing the adverse hepatic effects of pravastatin in rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2017.11.044DOI Listing
January 2018

High HPgV replication is associated with improved surrogate markers of HIV progression.

PLoS One 2017 14;12(9):e0184494. Epub 2017 Sep 14.

Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Background: Human Pegivirus (HPgV) may have a beneficial effect on HIV disease progression in co-infected patients; however, the virologic characteristics of this infection are not well defined. In this study, we determined HPgV viremia prevalence in Mexico and provide new insights to understand HPgV infection and HPgV/HIV co-infection.

Methods: We analyzed and quantified 7,890 serum samples for HPgV viremia by One-Step RT-Real-Time PCR, 6,484 from healthy blood donors and 1,406 from HIV-infected patients. Data on HIV progression were obtained from patients' records. HPgV genotyping was performed in 445 samples by nested PCR of the 5'URT region. Finite Mixture Models were used to identify clustering patterns of HPgV viremia in blood donors and co-infected antiretroviral (ART)-naïve patients.

Results: HPgV was detected in 2.98% of blood donors and 33% of HIV patients, with a wide range of viral loads. The most prevalent genotypes were 3 (58.6%)and 2 (33.7%). HPgV viral loads from healthy blood donors and HPgV/HIV+ ART-naïve co-infected patients were clustered into two component distributions, low and high, with a cut-off point of 5.07log10 and 5.06log10, respectively. High HPgV viremia was associated with improved surrogate markers of HIV infection, independent of the estimated duration of HIV infection or HIV treatment.

Conclusions: HPgV prevalence in Mexico was similar to that reported for other countries. The prevalent genotypes could be related to Mexico's geographic location and ethnicity, since genotype 2 is frequent in the United States and Europe and genotype 3 in Asia and Amerindian populations. HPgV viral load demonstrated two patterns of replication, low and high. The more pronounced beneficial response observed in co-infected patients with high HPgV viremia may explain discrepancies found between other studies. Mechanisms explaining high and low HPgV replication should be explored to determine whether the persistently elevated replication depends on host or viral factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184494PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598987PMC
October 2017

KIR2DL2 and KIR2DS2 as genetic markers to the methotrexate response in rheumatoid arthritis patients.

Immunopharmacol Immunotoxicol 2016 Aug;38(4):303-9

a Laboratorio de Inmunología, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;

Context: Disease Modifying Anti-Rheumatic Drugs (DMARDs) are aimed to interfere with rheumatoid arthritis (RA) progression and reduce the joint damage; however, not all patients respond alike. Killer-cell immunoglobulin-like receptors (KIR) and their ligands, human leucocyte antigen class I (HLA-I), have been associated with RA pathology; therefore, KIR and HLA genes may influence the treatment response.

Materials And Methods: We evaluated the association of KIR genotype and their ligands HLA-C genes with the response to DMARDs in RA patients. We included 69 patients diagnosed with RA and 82 healthy individuals as the reference group. KIR and HLA-C genotyping was performed using SSP-PCR. RA patients were assessed at baseline and under treatment at 6 and 12 months; subsequently classified as responders and non-responders in each time period. We evaluated the association between DMARD response and genes using statistical analysis by using Fisher exact test with Bonferroni correction; results were regarded as statistically significant at p < 0.05.

Results: Significant difference was observed in gene frequencies of patients and the reference group, KIR2DL2 was associated with RA (p = 0.031, OR = 2.119). We also observed an association between KIR2DS2 and the response to methotrexate (MTX), moreover, the combination KIR2DL2+/KIR2DS2+ was more frequent in responders to MTX (p = 0.043).

Discussion And Conclusions: In our results, responders and non-responders to DMARDs showed KIR2DS2 and KIR2DL2 different gene frequencies, therefore, these genes could be used as response predictors to DMARDs treatment. Thus, these genes were also associated with disease severity, as well as the treatment response possibly by the immunoregulatory function of NK cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08923973.2016.1194429DOI Listing
August 2016

Toll-like receptor-1 and receptor-2 and Beta-defensin in postcholecystectomy bile duct injury.

Gastroenterol Res Pract 2015 8;2015:216129. Epub 2015 Feb 8.

University Health Sciences Centre, University of Guadalajara, Avenida La Paz No. 2758, Colonia Arcos Sur, 44150 Guadalajara, JAL, Mexico.

Postcholecystectomy bile duct injuries (BDI) produce hepatic cholestasis and cause infection of the biliary tract. The biliary cells participate in secreting cytokines and in expression of immune response receptors. Toll-like receptors (TLRs) conduct signalling and activate the innate and adaptive inflammatory response. The objective was to determine the serum levels of TLR-2 and the expression of TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients. A transverse, analytical study with 2 groups was done. One group included healthy volunteers (control group) and other included 25 postcholecystectomy BDI patients with complete biliary obstruction. Using the Enzyme-linked Immunosorbent Assay (ELISA) technique, serum levels of TLR-2 were determined, and with immunofluorescence the morphologic analysis of TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients was performed. The average TLR-2 serum level in the control group was 0.0 pg/mL and in the BDI group, 0.023 ± 0.0045 pg/mL (P < 0.0001, bilateral Mann Whitney U). Immunofluorescence was used to determine the expression in liver biopsies, blood vessels, bile ducts, and hepatic parenchyma where 12 hepatic biopsies were positive for TLR-1 with average of 3213057.74 ± 1071019.25 μm(2); and 7 biopsies were positive for β-defensin with an average of 730364.33 ± 210838.02 μm(2); and 6 biopsies positive for TLR-2, obtaining an average of 3354364.24 ± 838591.06 μm(2). In conclusion, TLR-1 and TLR-2 and β-defensin play an important role in the innate antimicrobial defense of the hepatobiliary system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/216129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337755PMC
March 2015

Effect of nitaxozanide and pyrimethamine on astrocytes infected by Toxoplasma gondii in vitro.

Arch Med Res 2013 Aug 22;44(6):415-21. Epub 2013 Aug 22.

Laboratorio de Neurofisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, Mexico. Electronic address:

Background And Aims: T. gondii is a causal agent of encephalitis in immunocompromised patients. Pyrimethamine (PYR) has been the treatment of choice for toxoplasmosis. The aim of this study was to analyze the effect of nitazoxanide and pyrimethamine on astrocytes infected with T. gondii in vitro.

Methods: Rat astrocytes were cultured and infected with T. gondii. The effect of nitazoxanide (10, 20 and 30 μg/mL) and pyrimethamine (7, 10 and 13 μg/mL) on astrocytes infected was evaluated at 24 and 48 h post-infection. Tachyzoites and astrocytes were detected by the immunocytochemical method. T. gondii viability in astrocytes infected and treated with NTZ and PYR as well as NTZ and PYR cytotoxicity on astrocytes in vitro were evaluated by the MTT assay.

Results: The number of parasites in astrocytes treated with the drugs was significantly reduced when compared to control (p <0.001) at 24 and 48 h. Nitazoxanide produced 97% T. gondii death in a concentration of 10 μg/mL in 48 h infected astrocytes. At 48 h, the death rate of T. gondii was higher when treated with nitazoxanide than with pyrimethamine. A higher toxicity rate in astrocyte was observed when using pyrimethamine at 40 μg/mL.

Conclusions: Nitazoxanide reduced T. gondii infection more efficiently than pyrimethamine and is not cytotoxic to astrocytes at the administered dose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arcmed.2013.07.002DOI Listing
August 2013

YKL-40 expression in CD14⁺ liver cells in acute and chronic injury.

World J Gastroenterol 2011 Sep;17(33):3830-5

Department of Physiology, CUCS, University of Guadalajara, Guadalajara, Jalisco 44340, México.

Aim: To demonstrate that CD14⁺ cells are an important source of the growth factor YKL-40 in acute and chronic liver damage.

Methods: Rats were inoculated with one dose of CCl(4) to induce acute damage. Liver biopsies were obtained at 0, 6, 12, 24, 48 and 72 h. For chronic damage, CCl(4) was administered three days per week for 6 or 8 wk. Tissue samples were collected, and cellular populations were isolated by liver digestion and purified by cell sorting. YKL-40 mRNA and protein expression were evaluated by real-time polymerase chain reaction and western blot.

Results: Acute liver damage induced a rapid increase of YKL-40 mRNA beginning at 12 h. Expression peaked at 24 h, with a 26-fold increase over basal levels. By 72 h however, YKL-40 expression levels had nearly returned to control levels. On the other hand, chronic damage induced a sustained increase in YKL-40 expression, with 7- and 9-fold higher levels at 6 and 8 wk, respectively. The pattern of YKL-40 expression in different subpopulations showed that CD14⁺ cells, which include Kupffer cells, are a source of YKL-40 after acute damage at 72 h [0.09 relative expression units (REU)] as well as after chronic injury at 6 wk (0.11 REU). Hepatocytes, in turn, accounted for 0.06 and 0.01 REU after 72 h (acute) or 6 wk (chronic), respectively. The rest of the CD14⁻ cells (including T lymphocytes, B lymphocytes, natural killer and natural killer T cells) yielded 0.07 and 0.15 REU at 72 h and 6 wk, respectively. YKL-40 protein expression in liver was detected at 72 h as well as 6 and 8 wk, with the highest expression relative to controls (11-fold; P ≤ 0.05) seen at 6 wk. Macrophages were stimulated by lipopolysaccharide. We demonstrate that under these conditions, these cells showed maximum expression of YKL-40 at 12 h, with P < 0.05 compared with controls.

Conclusion: Hepatic CD14⁺ cells are an YKL-40 mRNA and protein source in acute and chronic liver injury, with expression patterns similar to growth factors implicated in inflammation-fibrogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v17.i33.3830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181445PMC
September 2011

[Tumor necrosis factor-alpha and interleukin-6 levels among patients suffering a bile duct injury during cholecystectomy].

Rev Med Chil 2010 Oct 10;138(10):1259-63. Epub 2011 Jan 10.

Departamento de Clínicas Quirúrgicas, Centro Universitario de Ciencias de la salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.

Background: During cholecystectomy, the bile duct may be injured. When this complication occurs, Kupffer cells are activated and produce tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL6) to phagocyte toxic products

Aim: To measure serum levels of TNF-α and IL-6 among patients that suffered a bile duct injury after a cholecystectomy.

Patients And Methods: Serum levels of TNF-α and IL-6 were measured prior to the bile-enteric derivation and after one year of follow up, in 31 patients that had a complete bile duct obstruction after open or laparoscopic cholecystectomy and in 5 healthy controls.

Results: At baseline TNF-α levels in healthy subjects and patients with bile duct injury were 0 and 43.9 ± 2.9 ng/mL, respectively (p < 0.01). At one year of follow up, TNF-á became undetectable among patients. At baseline, the values for IL-6 among healthy controls and patients were 3.0 ± 2.0 and 72.0 ± 94.7 pg/mL respectively, (p < 0,004). After one year of follow up, IL-6 levels decreased to 6.4 ± 0.3 pg/mL among patients.

Conclusions: TNF-α and IL-6 levels were elevated before bile-enteric derivation among patients with bile duct injury and became normal one year later.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org//S0034-98872010001100008DOI Listing
October 2010

The distribution of CD56(dim) CD16+ and CD56(bright) CD16- cells are associated with prolactin levels during pregnancy and menstrual cycle in healthy women.

Am J Reprod Immunol 2011 Apr 6;65(4):433-7. Epub 2010 Sep 6.

Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, CUCS, Universidad de Guadalajara, Jalisco, México.

Problem: The pregnancy and menstrual cycle (MC) are the main physiologic events linked to the human reproduction. An adequate neuroendocrine axis is mandatory for the homeostasis in both events. To analyze the distribution of NK, T, Treg cells, expression of their receptors and to associate with hormone levels in pregnant and MC in healthy women.

Method Of Study: We studied two groups of healthy women: 13 pregnant women followed up at 1st, 2nd and 3rd trimesters and 11 women in the 5th and 21st day of the MC. The distribution of NK, T, Treg cells population, expression of their receptors and hormone levels were quantified.

Results: In pregnant women, we found an association of NK cells CD56(dim) CD16(+) with prolactin levels. This finding was also was observed for CD56(brigthCD16-) being statistical significant during 1st trimester for both subpopulations. During MC, correlation of CD56(dim) CD16(+) , CD56(bright) CD16(-) cells with prolactin in follicular and luteal phase was found.

Conclusion: This is the first report where these cell subpopulations have been analyzed prospectively. Even we can argue the random effect for the small number of women is interesting that prolactin showed the more consistent correlation with CD56(dim) CD16(+) , CD56(brigth) CD16(-) cells during both events studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0897.2010.00916.xDOI Listing
April 2011

Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions.

BMC Cancer 2009 Jun 16;9:186. Epub 2009 Jun 16.

Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No 950, Colonia Independencia, Guadalajara, Jalisco, Mexico.

Background: Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.

Methods: NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.

Results: We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.

Conclusion: Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2407-9-186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704222PMC
June 2009

[Effect of the nutritional recovery on the concentration of Interleukin-2 in severely malnourished children].

Arch Latinoam Nutr 2008 Jun;58(2):144-8

Instituto de Nutrición Humana & Laboratorio de Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara México.

The severely malnourished child has dysfunction of the immune response that may increase the risk of morbidity or mortality due to infectious diseases, therefore, the purpose of this study was to demonstrate the effect of intensive nutritional support on the cellular and serum concentration of IL-2 and CD4+, as well as CD8+ T cells in children with severe protein energy malnutrition. A clinical assay was carried out in a tertiary care hospital. 10 severely malnourished children < 48 months of age who received formula without lactose via enteral feeding for two weeks and ad libitum for an additional two weeks were included. Cellular and serum concentrations of IL-2 and the subpopulation of CD4+ and CD8+ were obtained. A control group (n = 13) was included. A paired student t test for initial-final determinations and the Mann-Whitney Test for comparison with control group were used, and null hypothesis was rejected with a p value < 0.05. There was a noteworthy increase in the comparison between the initial vs. final percentage of the cellular expression of IL-2 (p < 0.001) and in the serum concentration of IL-2 (p = 0.001). Therefore, four weeks of nutritional recovery significantly restored the production of IL-2, independently of the nutrients involved in the process, although, the rate of restoration seems to depend on the severity of the children primary PEM.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2008

[Lymphocyte subsets and preeclampsia].

Ginecol Obstet Mex 2008 Jun;76(6):327-35

Centro Médico Nacional de Occidente, UMAE, Hospital de Especialidades, Unidad de Investigación Médica en Epidemiología Clínica, Guadalajara, Jalisco, México.

Background: Preeclampsia origin has no conclusive explanation. As part of its etiology it has been proposed immunologic disorders. This work explores several lymphocytes subsets and postulates possible mechanisms involved in a lost of immune tolerance in this entity.

Objective: To compare cellular populations of CD3+ CD56+, CD4+ CD25+, T lymphocytes (CD4+ and CD8+) and NK cells subsets in preeclamptic and pregnant healthy women.

Patients And Methods: Through flow cytometry antibodies, peripheral blood mononuclear cells were obtained from both groups of patients. CD3+ CD56+, CD4+ CD25+, T lymphocytes (CD4+ and CD8+) and NK cells were identified. Mean and standard deviation, Student ttest and Pearson correlation were calculated to analyze differences between groups and correlation between mean blood pressure and different lymphocytes subsets; p < 0.05 was considered significant.

Results: CD3+ CD56+ cells percentage was lower in preeclamptic patients (2.7 vs 6.1%; p < 0.002), CD4+ CD25+ cells percentage tend to be lower too (22.11 vs 33.86; p = NS). Mean blood pressure shown negative correlation with CD3+ CD56+ cells percentage (rp - 0.666; p = 0.001) and with CD25 on CD4+ T lymphocytes surface (rp - 0.526; p < 0.025).

Conclusions: Based on the association between mean blood pressure and lymphocytes percentage for these two cellular subsets, data obtained suggest that CD3+ CD56+ and CD4+ CD25+ cells play an important role in preeclampsia development.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2008

Expression of NK cells activation receptors after occupational exposure to toxics: a preliminary study.

Immunol Lett 2008 Jun 22;118(2):125-31. Epub 2008 Apr 22.

Environmental Immunology Laboratory, Western Biomedical Research Center of the Mexican Institute for Social Security, Guadalajara, Jalisco, Mexico.

The expression of NK cells activation receptors was assessed by comparative study of two groups of women workers at a chemical reagents factory, located in Zapopan, Jalisco, Mexico. Twenty of them were exposed to environmental toxics identified and quantified by gas chromatography, and 20 women unexposed to toxic substances. The expression of the surface markers CD56+ and CD3+, and of the activation receptors and co-receptors on NK cells was quantified by flow cytometry. To assess the cellular damage produced by chronic exposure to the toxics, the thiobarbituric acid reacting substances (TBARS) generated and the total plasma antioxidizing capacity (TPAC) were quantified in both groups. The exposed women had been exposed at least to 12 volatile toxic compounds, benzene, benz(a)pyrene, ethylbenzene, dimethylbenz(a)anthracene, xylene, toluene, styrene, chloroform, formaldehyde, iodine, chlorine and fluorine. Significant difference between the two groups was in the proportion of CD3 lymphocytes, 72.7+/-10.3% in the unexposed women versus 66.8+/-7.9% in the exposed group (p<0.05). The density of expression of NKG2D and NKp30 receptors was significantly higher in the unexposed women compared to the exposed group: NKG2D were 31.3+/-6.3 and NKp30 were 9.5+/-5.2 in the unexposed women and 5.14+/-2.9 (p<0.01) and 4.6+/-1.9 (p<0.05), respectively in the exposed women. No statistically significant differences were found in the expression of NKp80, NKp46 and 2B4 receptors. The concentration of TBARS was lower in women from the unexposed group than the corresponding data from women of the exposed group. However, no significant difference was observed in TPAC between the two groups studied. The results of this preliminary study suggest that from the five activation receptors and co-receptors of NK cells evaluated (NKp30, NKp46, NKp80, NKG2D and 2B4), only NKp30 and NKG2D receptor expression was diminished in women exposed to toxics when compared with data from unexposed women. These results suggest that the occupational exposure to mixture of toxics is one of the important factors in the diminution of the NK cell receptor expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2008.03.010DOI Listing
June 2008

Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions.

BMC Cancer 2008 Jan 21;8:16. Epub 2008 Jan 21.

Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.

Background: Cervical cancer is the second most common cancer in women worldwide. NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Increased serum levels of MICA have been found in patients with epithelial tumors. The aim of this study was to compare the levels of soluble MICA (sMICA) and NKG2D-expressing NK and T cells in blood samples from patients with cervical cancer or precursor lesions with those from healthy donors.

Methods: Peripheral blood with or without heparin was collected to obtain mononuclear cells or sera, respectively. Serum sMICA levels were measured by ELISA and NKG2D-expressing immune cells were analyzed by flow cytometry. Also, a correlation analysis was performed to associate sMICA levels with either NKG2D expression or with the stage of the lesion.

Results: Significant amounts of sMICA were detected in sera from nearly all patients. We found a decrease in the number of NKG2D-expressing NK and T cells in both cervical cancer and lesion groups when compared to healthy donors. Pearson analysis showed a negative correlation between sMICA and NKG2D-expressing T cells; however, we did not find a significant correlation when the analysis was applied to sMICA and NKG2D expression on NK cells.

Conclusion: Our results show for the first time that high sMICA levels are found in sera from patients with both cervical cancer and precursor lesions when compared with healthy donors. We also observed a diminution in the number of NKG2D-expressing NK and T cells in the patient samples; however, a significant negative correlation between sMICA and NKG2D expression was only seen in T cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2407-8-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270854PMC
January 2008

Protease-activated receptor-2 (PAR-2) in cervical cancer proliferation.

Gynecol Oncol 2008 Jan 23;108(1):19-26. Epub 2007 Oct 23.

Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No 950, Colonia Independencia, Guadalajara, Jalisco, CP 44340, Mexico.

Objective: Protease-activated receptor-2 (PAR-2) is a G-protein-coupled receptor that is cleaved and activated by trypsin and tryptase. There is evidence that PAR-2 contributes to tumor progression in stomach, colon, pancreas, prostate and breast cancer patients. However, the role of PAR-2 in cervical cancer is still unknown. The aim of this work was to study the PAR-2 expression in cervical cancer tissues and the effect of PAR-2 activation on cervical cancer proliferation.

Methods: Immunohistochemistry was used to analyze PAR-2 expression in fixed paraffin-embedded tumor tissue from 16 patients with invasive cervical cancer. HPV types were identified by PCR. PAR-2 expression in UISO-SQC-1, HeLa, SiHa, CasKi and C-33 A cervical cancer cell lines was evaluated by flow cytometry. Trypsin was detected by Western blot. Tumor proliferation in response to trypsin or agonist peptide was evaluated by the MTT method.

Results: A strong correlation between trypsin and PAR-2 expression in five cervical cancer cell lines, in association with proliferative growth in the presence of trypsin or agonist peptide, was found. All tumors from cervical cancer patients expressed PAR-2 (immunoreactive score was higher in poorly differentiated tumors).

Conclusions: Results suggest that trypsin and PAR-2 are involved in cervical cancer cell proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2007.08.083DOI Listing
January 2008

Effect of renutrition on natural and cell-mediated immune response in infants with severe malnutrition.

J Pediatr Gastroenterol Nutr 2002 Mar;34(3):296-301

Instituto de Nutrición Humana, Crecimiento y Desarrollo Infantil, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Background: The purpose of this study was to evaluate whether a 4-week nutritional recovery period with a starting infant formula and 3.35 kJ/mL energy density would favorably affect the natural and cell-mediated immune response in infants with severe and primary protein-energy malnutrition.

Methodology: The study included 12 severely malnourished infants, 3 to 18 months of age. For 2 weeks, infants were fed a starting infant formula, with energy density increased to 0.8 kcal/mL, through a nasogastric tube. Infants were fed "ad libitum" for 2 more weeks. On the fifth day, 837 kJ/kg and 4 g/kg protein were given daily. At the beginning and at the end of the 4-week period, weight, length, phagocytosis, microbicidal activity, chemotaxis, and cell proliferation indices were measured. Null hypothesis was rejected with a paired t test and a P value less than 0.05.

Results: After the 4-week period of nutritional recovery, the weight and length indicators and the four immunologic assays showed significant increase (P < 0.005).

Conclusion: The study demonstrated that a 4-week nutritional recovery period with a starting infant formula and 0.8 kcal/mL energy density favorably affected the natural and cell-mediated immune response in infants with severe protein-energy malnutrition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00005176-200203000-00015DOI Listing
March 2002

Interleukin 1beta (IL-1beta), IL-10, tumor necrosis factor-alpha, and cellular proliferation index in peripheral blood mononuclear cells in patients with ankylosing spondylitis.

J Rheumatol 2002 Mar;29(3):522-6

Instituto de Biología Molecular en Medicina, Universidad de Guadalajara, Jalisco, México.

Objective: To evaluate cytokine production and cellular proliferation index (CPI) in peripheral blood mononuclear cells (PBMC) of patients with ankylosing spondylitis (AS), and their association with clinical variables.

Methods: In a cross sectional study we compared the production of tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-10 and CPI in response to phytohemagglutinin (PHA) in PBMC of 27 patients with AS and 24 healthy controls. We also assessed clinical characteristics including disease activity index (BASDAI) and functional index (BASFI).

Results: Levels of IL-1beta were higher in patients with AS (median 242 pg/ml) than in controls (median 65 pg/ml); p = 0.002. No differences were observed in median levels of TNF-alpha or IL-10 between AS and controls. Patients had a reduction in CPI (1.2 in AS vs 1.8 in controls; p < 0.001). A positive correlation was observed between IL-10 production and age (rho = 0.34, p = 0.01). A borderline negative correlation was observed between CPI and age (rho = -0.26, p = 0.07).

Conclusion: Patients with AS had high production of IL-1beta compared with controls and a poor response in CPI. These findings may explain the lack of response for microbial antigens mediated by the innate immune response.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2002