Publications by authors named "Alireza Rezaiemanesh"

21 Publications

  • Page 1 of 1

Retinoic Acid Correlates with Reduced Serum IL-10 And TGF-β in Allergic Rhinitis.

Rep Biochem Mol Biol 2021 Jan;9(4):399-407

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Retinoic acid (RA) plays a key role in naïve T cell differentiation into FOXP3+ Treg cell in the respiratory airways. The present study aims to investigate RA and Treg-related cytokine serum levels, salivary IgA levels, FOXP3 and IL-4 gene expression, and the relationships between RA serum levels and Treg-related cytokines in allergic rhinitis (AR) patients and healthy controls.

Methods: Salivary IgA and serum IgE, RA, IL-10, and TGF-β concentrations were measured by ELISA in 37 AR patients and 30 age- and sex-matched healthy controls.

Results: IL-10 and TGF-β concentrations were significantly less in AR patients than in healthy controls (p< 0.01 and P< 0.0001, respectively). Salivary IgA was significantly greater in patients than in controls (p< 0.05). RA was not significantly different between patients and controls (p> 0.05); however, a significant positive correlation was found between serum RA and both IL-10 and TGF-β in AR patients.

Conclusion: Our data suggest that RA may influence AR risk via affecting the TGF-β and IL-10 production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.52547/rbmb.9.4.399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068451PMC
January 2021

Association of interleukin-12B rs6887695 with susceptibility to allergic rhinitis.

Immunol Res 2021 Apr 8;69(2):189-195. Epub 2021 Apr 8.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Interleukin-12 (IL-12) is a heterodimeric cytokine encoded by two separate genes, IL12A and IL12B, which may play a regulatory role in allergen-induced inflammation through CD4 T-cell subsets polarization. The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) in the IL12B gene with susceptibility to allergic rhinitis (AR). We performed a case-control study including 130 AR patients and 130 healthy controls to evaluate the possible association between IL12B gene SNPs (rs3212227, rs6887695) and the risk of AR using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our results showed no significant association between IL12B rs3212227 A > C polymorphism with AR. In contrast, the GC genotype of rs6887695 G > C was associated with susceptibility to AR in comparison with the GG genotype (p = 0.049, OR = 1.684, 95% CI: 1.002-2.83). We also observed a statistically significant difference in the additive model (GC versus GG + CC, p = 0.03, OR = 1.705, 95% CI: 1.040-2.794) for SNPs rs6887695. Furthermore, haplotypes analysis demonstrated that C-C haplotype was associated with an increased risk of AR (p = 0.01, OR = 1.845, 95% CI: 1.114-3.057). Our findings suggest that IL12B rs6887695 polymorphism may be a potential biomarker for susceptibility to AR in an Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12026-021-09189-1DOI Listing
April 2021

Determination of the transcriptional level of long non-coding RNA NEAT-1, downstream target microRNAs, and genes targeted by microRNAs in diabetic neuropathy patients.

Immunol Lett 2021 Apr 27;232:20-26. Epub 2021 Jan 27.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Background: Diabetic neuropathy (DN) is one of the microvascular complications of diabetes that leads to peripheral sensorimotor and autonomic nervous system damages. In this study, we first examined the expression of lncRNA NEAT-1 and its downstream microRNAs, miR-183-5p, miR-433-3p, and then examined mRNA expression of ITGA4, ITGB1, SESN1, and SESN3 as the downstream targets of miR-183-5p, miR-433-3p.

Methods: The blood sample was obtained from a total of 40 patients with type 2 diabetes (20 DN patients and 20 non-DN diabetic cases) and ten healthy individuals. After RNA extraction from peripheral blood samples and cDNA synthesis, expression measurements were performed by the RT-qPCR technique.

Results: Our results showed that the expression level of lncRNA NEAT-1 was significantly higher, and the expression level of miR-183-5p was significantly lower in DN patients compared to the healthy control group. Besides, the expression level of miR-433-3p was significantly lower, and the mRNA expression of ITGA4, SESN1, and SESN3 was significantly higher in DN patients compared to the diabetes group. The ROC curve analysis showed that the miR-183-5p with high levels of accuracy could discriminate DN patients from healthy control (AUC = 0.836) and NEAT-1, SESN1, SESN3, ITGA4 have a high ability to distinguish DN from non-DN patients (AUC = 0.701, 0.772, 0.815 and 0.780, respectively).

Conclusion: It seems that the NEAT-1 probably targets miR-183-5p and miR-433-3p, as a result of which the expression of ITGA4, SESN1, and SESN3 is affected. Dysregulated expression of NEAT-1 and related miRNAs and genes might be involved in the pathogenesis of DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2021.01.007DOI Listing
April 2021

Imbalanced serum levels of resolvin E1 (RvE1) and leukotriene B4 (LTB4) in patients with allergic rhinitis.

Mol Biol Rep 2020 Oct 22;47(10):7745-7754. Epub 2020 Sep 22.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, PO-Box: 6714869914, Kermanshah, Iran.

Timely and successful resolution of acute inflammation plays a crucial role in preventing the development of chronic airway inflammation in allergic rhinitis (AR). This study intends to assess the serum levels of pro-inflammatory leukotriene B4 (LTB4), anti-inflammatory mediators, including resolvin E1 (RvE1), RvD1, IL-10, and TGF-β, besides mRNA expression level of G-protein coupled receptor 120 (GPR120) and peroxisome proliferator-activated receptor-γ (PPAR-γ) receptors in peripheral blood leukocytes of AR patients. Thirty-seven AR patients and thirty age- and gender-matched healthy subjects were enrolled in this study. The serum levels of LTB4, RvE1, RvD1, IL-10, and TGF-β were measured using enzyme-linked immunosorbent assay (ELISA) technique, and the mRNA expression level of GPR120 and PPAR-γ was assessed by the real-time PCR method. The serum levels of RvE1 and LTB4 were significantly higher in patients with AR than in healthy subjects (P < 0.01 and P < 0.0001, respectively). However, a significantly lower ratio of RvE1 and RvD1 to LTB4 was found in patients with AR relative to healthy subjects (P < 0.05 and P < 0.0001, respectively). Likewise, the serum levels of both IL-10 and TGF-β cytokines were significantly reduced in patients with AR compared to healthy subjects (P < 0.01 and P < 0.0001, respectively). Furthermore, the mRNA expression of PPAR-γ was significantly lower in patients with AR than in healthy subjects (P < 0.05). Our findings indicate that imbalanced pro-resolving lipid mediator RvE1 and pro-inflammatory LTB4 might contribute to the defective airway inflammation-resolution and subsequent progression toward chronic inflammation in AR patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-020-05849-xDOI Listing
October 2020

Semaphorin 4A, 4C, and 4D: Function comparison in the autoimmunity, allergy, and cancer.

Gene 2020 Jul 31;746:144637. Epub 2020 Mar 31.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Semaphorins are a group of proteins that are divided into eight subclasses and identified by a conserved Sema domain on their carboxyl terminus. Sema4A, 4C, and 4D are the members of the fourth class of semaphorin family, which are known as membrane semaphorins; however, these molecules can be altered to soluble semaphorins by proteolytic cleavage. Semaphorins have various roles in the immune, nervous, and metabolic systems. In the immune system, these molecules contribute to the formation of cellular, humoral, and innate immune responses, such as inflammation, leukocyte migration, immunological synapse formation, and germinal center events. Given the diverse roles of semaphorins in the immune system, in this review, we have tried to give a comprehensive look at the role of these molecules in autoimmunity, allergy, and cancer. Sema4D and 4A seem to play a critical role in the pathogenesis of some autoimmune diseases, such as multiple sclerosis. In contrast, it has been shown that Sema4A and 4C have beneficial effects on allergies, and their absence can exacerbate the severity of the disease. In the case of cancer, an increase in all three of these molecules has been reported. Sema4D and 4C can contribute to tumor progression in human patients or experimental models, while the role of Sema4A has not yet been fully understood. In conclusion, semaphorins seem to be a favorable therapeutic target for autoimmune diseases and allergies. However, in cancer, studies have not yet been able to identify the exact role of semaphorins, and further studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2020.144637DOI Listing
July 2020

P2 receptors mRNA expression profiles in macrophages from ankylosing spondylitis patients and healthy individuals.

Int J Rheum Dis 2020 Mar 29;23(3):350-357. Epub 2019 Dec 29.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Ankylosing spondylitis (AS) is a multifactorial rheumatic disease which mainly involves the axial skeleton. Macrophages and extracellular nucleotides have been shown to contribute to the inflammation process in autoimmune diseases. Membrane-bound purinergic P2 receptors might be involved in the modulation of immune cells in AS. Therefore, we aimed to analyze the messenger RNA (mRNA) expression of P2 receptors in the macrophages of AS patients and healthy controls.

Methods: Twenty-three AS patients and 23 age- and sex-matched healthy individuals were included in our study. Whole blood-separated monocytes of study participants were stimulated by macrophage colony-stimulating factor for 7 days and differentiated to macrophages. Monocyte and macrophage markers were analyzed by flow cytometry. SYBR green real-time polymerase chain reaction was used to measure the relative expression levels of P2RX , P2RX , P2RX , P2RX , P2RX , P2RX , P2RX , P2RY , P2RY , P2RY , P2RY , P2RY , P2RY , P2RY , P2RY , and PANX1 genes.

Results: P2RY and P2RY genes had the highest expression levels in macrophages among P2RY genes. P2RY mRNA expression was significantly down-regulated (-1.75 fold) and P2RY was up-regulated (2.6 fold) in macrophages of AS patients compared to healthy individuals. P2RX gene had the highest expression in monocyte-derived macrophages, followed by P2RX and P2RX genes. There was no significant difference in P2X receptor mRNA expression level between macrophages of AS patients and healthy individuals.

Conclusions: Our results indicate that AS patients show altered expression levels of P2 receptor genes. Moreover, these changes might be associated with disease activity and patients' status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1756-185X.13783DOI Listing
March 2020

Regulatory T cells for amyotrophic lateral sclerosis/motor neuron disease: A clinical and preclinical systematic review.

J Cell Physiol 2020 06 1;235(6):5030-5040. Epub 2019 Dec 1.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by neuronal degeneration and inflammation in the nerves. The role of the immune system has been concentrated by researchers in the etiopathogenesis of the disease. Given the inhibitory roles of regulatory T cells (Tregs), it is expected that increasing or activating their populations in patients with ALS can have significant therapeutic effects. Here we searched databases, including CENTRAL, MEDLINE, CINAHL Plus, clinicaltrials.gov, and ICTRP for randomized clinical trials (RCTs) and non-RCTs until March 2019. For preclinical studies, we searched PubMed, Scopus, and Google Scholar up to June 2019. We also included preclinical studies, due to the lack of clinical information available, which used Tregs (or directly targeting them) for treating mice models of ALS. We identified 29 records (CENTRAL 7, MEDLINE 4, CINAHL Plus 8, and clinicaltrials.gov 10) and removed 10 duplicated publications. After screening, we identified one RCT which had been published as an abstract, three non-RCTs, and four ongoing studies. We also identified 551 records (PubMed 446, Google Scholar 68, and Scopus 37) for preclinical studies and performed a meta-analysis. Finally, we found three papers that matched our inclusion criteria for preclinical studies. Results indicated the effectiveness of the application of Tregs in the treatment of ALS. Our meta-analysis on preclinical studies revealed that Tregs significantly prolonged survival in mice models of ALS. Overall, our analysis testified that exertion of Tregs in the treatment of ALS is a promising approach, that notwithstanding, requires further evaluations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.29401DOI Listing
June 2020

Evaluation of ERAP1 gene single nucleotide polymorphisms in immunomodulation of pro-inflammatory and anti-inflammatory cytokines profile in ankylosing spondylitis.

Immunol Lett 2020 01 9;217:31-38. Epub 2019 Nov 9.

Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Connective Tissue Research Center, Tabriz University of Medical Science, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Background: Ankylosing spondylitis (AS) is a prototype of chronic inflammatory arthritis termed seronegative spondyloarthropathies that typically affects the joints. Among the non-Human leukocyte antigen (HLA) loci, the strongest association has been observed with Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene single nucleotide polymorphisms (SNPs). Moreover, the effect of ERAP1 gene SNPs on the pro-inflammatory and anti-inflammatory cytokines in AS disease has still been poorly elucidated. In this study, we aimed to determine the association of ERAP1 gene SNPs (rs30187 and rs2287987) with AS risk as well as their effect on the mRNA expression of pro-inflammatory and anti-inflammatory cytokines, with emphasis on the immunoregulation of the IL-17/IL-23 pathway, in an Iranian population.

Methods: We performed Single specific primer (SSP)-PCR for genotyping of 160 AS patients and 160 healthy controls. After isolation of peripheral blood mononuclear cells (PBMCs), total RNA of PBMCs was isolated, complementary DNA (cDNA) was synthesized, and quantitative analyses of mRNA expression of cytokines were performed by Real-time PCR for 40 HLA-B27 positive AS patients and 40 healthy individuals as controls.

Results: It was seen that T allele of rs30187 (OR = 1.54, 95% CI = 1.07-2.22, P =  0.017) and C allele of rs2287987 (OR 1.50, 95% CI 1.05-2.14, P = 0.024) were associated with the risk of AS. Both of these alleles were associated more strongly in the HLA-B27 positive AS patients. There was a significant overexpression of mRNAs of pro-inflammatory (IL-17A, IL-17F, IL-23, TNF-α and IFN-γ), while downregulation of anti-inflammatory cytokines (IL-10 and TGF-β) in PBMCs from 40 HLA-B27 positive AS patients in comparison to controls. AS patients with rs30187 SNP TT genotype expressed mRNA of IL-17A, IL-17F, and IL-23 significantly higher than patents with CT and CC genotypes for this SNP.

Conclusions: This study represented the association of ERAP1 gene rs30187 and rs2287987 polymorphism with the risk of AS. Additionally, it appears that rs30187 polymorphism may be involved in the immunomodulation of the IL-17/IL-23 pathway in the AS disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2019.10.016DOI Listing
January 2020

The role of myeloid-derived suppressor cells in the pathogenesis of rheumatoid arthritis; anti- or pro-inflammatory cells?

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):4149-4158

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of the immature myeloid cells that are derived from the myeloid progenitors with immunosuppressive functions. MDSCs are accumulated in the inflammatory sites during some autoimmune disorders, such as rheumatoid arthritis (RA) and can be an important factor in the pathogenesis of these diseases. Some research has shown the anti-inflammatory role of MDSCs during the RA progression and supports the hypothesis that MDSCs can be a potential treatment option for autoimmunity with their immunosuppressive activity. In contrast, some papers have reported the opposite effects of MDSCs, and support the hypothesis that MDSCs have a pro-inflammatory role in autoimmune disease. MDSCs functions in RA have not been fully understood, and some controversies, as well as many unanswered questions, remain. Although the two well-known subgroups of MDSCs, M-MDSC, and PMN-MDSC, seem to have different suppressive functions and regulate the immune system responses in a different manner; some studies have shown these cells are converted to each other and even to other cells under different pathological conditions. This review summarises some of the latest papers with respect to the MDSCs functions and discusses the relationship between MDSCs and inflammation in the context of rheumatoid arthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2019.1687504DOI Listing
December 2019

Epigenetic changes in gastric cancer induction by Helicobacter pylori.

J Cell Physiol 2019 12 6;234(12):21770-21784. Epub 2019 Jun 6.

Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran.

Epigenetic disorder mechanisms are one of the causes of cancer. The most important of these changes is the DNA methylation, which leads to the spread of Helicobacter pylori and inflammatory processes followed by induction of DNA methylation disorder. Mutations and epigenetic changes are the two main agents of neoplasia. Epithelial cells infection by H. pylori associated with activating several intracellular pathways including: MAPK, NF-κB, Wnt/β-catenin, and PI3K are affects a variety of cells and caused to an increase in the production of inflammatory cytokines, changes in apoptosis, proliferation, differentiation, and ultimately leads to the transformation of epithelial cells into oncogenic. The arose of free radicals impose the DNA cytosine methylation, and NO can increase the activity of DNA methyltransferase. H. pylori infection causes an environment that mediates inflammation and signaling pathways that probably caused to stomach tumorigenicity. The main processes that change by decreasing or increasing the expression of various microRNAs expressions include immune responses, apoptosis, cell cycle, and autophagy. In this review will be describe a probably H. pylori roles in infection and mechanisms that have contribution in epigenetic changes in the promoter of genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.28925DOI Listing
December 2019

Ankylosing spondylitis and mesenchymal stromal/stem cell therapy: a new therapeutic approach.

Biomed Pharmacother 2019 Jan 6;109:1196-1205. Epub 2018 Nov 6.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Ankylosing spondylitis (AS) is an inflammatory rheumatoid disease categorized within spondyloarthropathies (SpA) and manifested by chronic spinal arthritis. Several innate and adaptive immune cells and secreted-mediators have been indicated to play a role in AS pathogenesis. Considering the limitations of current therapeutic approaches (NSAIDs, glucocorticoids, DMARDs and biologic drugs), finding new treatments with fewer side effects and high therapeutic potentials are required in AS. Mesenchymal stem cells (MSCs) with considerable immunomodulatory and regenerative properties could be able to attenuate the inflammatory responses and help tissue repair by cell-to-cell contact and secretion of soluble factors. Moreover, MSCs do not express HLA-DR, which renders them a favorable therapeutic choice for transplantation in immune-mediated disorders. In the present review, we describe immunopathogenesis and current treatments restrictions of AS. Afterwards, immunomodulatory properties and applications of MSCs in immune-mediated disorders, as well as recent findings of clinical trials involving mesenchymal stem cell therapy (MSCT) in ankylosing spondylitis, will be discussed in detail. Additional studies are required to investigate several features of MSCT such as cell origin, dosage, administration route and, specifically, the most suitable stage of disease for ideal intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2018.10.137DOI Listing
January 2019

Evaluation of ERAP1 Gene Single Nucleotide Polymorphism in Impressing the Inflammatory Cytokine Profile of Ankylosing Spondylitis Patients.

Iran J Allergy Asthma Immunol 2018 Oct 20;17(5):464-474. Epub 2018 Oct 20.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran AND Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

Ankylosing spondylitis (AS), an autoinflammatory disease, has been associated with impaired Endoplasmic reticulum aminopeptidase (ERAP) 1 activity, which is involved in priming antigenic peptides. The purpose of this study was to evaluate if the genetic variant of ERAP1 gene could impress the inflammation status of the AS patients. For genotyping, 140 AS cases and 140 healthy controls were enrolled. After isolation of peripheral blood mononuclear cells (PBMCs) and DNA extraction, all the subjects were genotyped for rs27044 polymorphism using SSP-PCR assay. Total RNA of PBMCs was isolated, cDNA was synthesized, and quantitative analyses of mRNA expression of cytokines were performed via Real-time PCR using the SYBR Green Gene Expression MasterMix. To measure the concentration of cytokines in serum of subjects, Enzyme-linked immunosorbent assay (ELISA) was used. It was observed that the G allele of rs27044 polymorphism was significantly prevalent in AS patients. Moreover, the GG genotype and the GG+GC dominant model had significantly different distribution between study groups. There was a significant overexpression of mRNAs of IL-17A, IL-6, IL-33, TNF-α, and IFN-γ, while IL-10 was significantly downregulated in AS patients. The ELISA results were in line with that of the gene expression analysis. No significant differences in mRNA expression and concentration of cytokine were identified among AS patients with three genotypes for rs27044 SNP. This study replicated the association of polymorphisms in ERAP1 gene with the risk of AS in a population from Iranian. However, it did not directly determine the inflammatory profile of the AS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2018

Immunoresolvents in asthma and allergic diseases: Review and update.

J Cell Physiol 2019 06 29;234(6):8579-8596. Epub 2018 Nov 29.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Asthma and allergic diseases are inflammatory conditions developed by excessive reaction of the immune system against normally harmless environmental substances. Although acute inflammation is necessary to eradicate the damaging agents, shifting to chronic inflammation can be potentially detrimental. Essential fatty-acids-derived immunoresolvents, namely, lipoxins, resolvins, protectins, and maresins, are anti-inflammatory compounds that are believed to have protective and beneficial effects in inflammatory disorders, including asthma and allergies. Accordingly, impaired biosynthesis and defective production of immunoresolvents could be involved in the development of chronic inflammation. In this review, recent evidence on the anti-inflam]matory effects of immunoresolvents, their enzymatic biosynthesis routes, as well as their receptors are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.27836DOI Listing
June 2019

Curcumin reduces the expression of interleukin 1β and the production of interleukin 6 and tumor necrosis factor alpha by M1 macrophages from patients with Behcet's disease.

Immunopharmacol Immunotoxicol 2018 Aug 28;40(4):297-302. Epub 2018 May 28.

a Rheumatology Research Center , Tehran University of Medical Sciences , Tehran , Iran.

Objective: Behcet's disease (BD) is an auto-inflammatory disorder. Curcumin as a bio-active agent has anti-inflammatory properties. Effects of curcumin on the pathogenesis of BD are still not clear. In this study, we investigated the effect of curcumin on the inflammatory cytokines expression and production in M1 macrophages from BD patients compared with healthy controls.

Methods: Monocytes were collected from 10 healthy controls and 20 active BD patients, differentiated to macrophages by macrophage-colony stimulating factor for 7 d. Macrophages were then treated with interferon gamma, lipopolysaccharide, and curcumin (10 or 30 µg/ml) for 24 h. Analysis of tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), and IL-6 mRNA expression and protein production was performed using SYBR Green qPCR and ELISA method.

Results: Treatment with 30 µg/ml curcumin significantly down-regulated mRNA expression of IL-1β (p < .05) and protein production of IL-6 (p < .05) in M1 macrophages from BD patients but not in M1 macrophage from controls. Treatment with 30 µg/ml curcumin also significantly diminishes the protein production of TNFα in BD patients (p < .01) and healthy controls (p < .05) M1 macrophages.

Conclusions: We demonstrated that curcumin can inhibit the expression and production of inflammatory cytokines in M1 macrophages from BD patients. Our results suggest that curcumin can modulate inflammatory signaling more specifically in macrophages from BD patients than healthy macrophages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08923973.2018.1474921DOI Listing
August 2018

Immune cells involved in the pathogenesis of ankylosing spondylitis.

Biomed Pharmacother 2018 Apr 16;100:198-204. Epub 2018 Feb 16.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Ankylosing spondylitis (AS) is an inflammatory autoimmune disease. AS is a prototype form of spondyloarthropathies (SpA). The precise etiology of AS has not been fully understood. But Inflammation has a critical role in the pathogenesis of the disease. The immune system by various cells, secreted-mediators and markers manage and regulate the immune responses and inflammation. Every factor which disturbed this regulation and hemostasis can cause chronic inflammation. In this review, we discussed the role of several innate and adaptive immune cells involved in the triggering, initiation, development, and regulation of AS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2018.01.108DOI Listing
April 2018

The role of gut microbiota and IL-23/IL-17 pathway in ankylosing spondylitis immunopathogenesis: New insights and updates.

Immunol Lett 2018 04 2;196:52-62. Epub 2018 Feb 2.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Ankylosing spondylitis (AS) is a type of arthritis that is referred to a group of chronic immune-mediated inflammatory diseases termed as seronegative spondyloarthropathies or spondyloarthritides. It typically affects the joints of the spinal and axial skeleton and exhibits common clinical features and genetic factors such as human leukocyte antigen class I allele HLA-B27, the Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), and environmental factors such as microbial triggers. Although the precise etiopathogenic mechanisms that implicate the pathogenesis of AS have still remained to be clarified, the IL-23/IL-17 immune axis has been detected as an important factor in the immunopathogenesis of AS. Moreover, therapeutic options targeting this signaling pathway have been demonstrated to be effective in various other inflammatory diseases that share similar genetic etiology and pathogenetic pathways. In mammalian intestinal, there are trillions of commensal microbes that create the intricate symbiotic relationship with host well-known as the microbiota and play the major role in human health and disease. Several publications have appeared in recent years documenting the pivotal role of the gut microbiota and the IL-23/IL-17 pathway in the pathogenesis of spondyloarthritides. In this review, several points are discussed and summarized including recent advances on the role of the IL-17/IL-23 immune pathway in the pathogenesis of AS, HLA-B27, and ERAP 1 and 2 mediated pathogenesis, AS-related microbiota compositions, and new potential therapies for AS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2018.01.014DOI Listing
April 2018

PDCD1 Single Nucleotide Polymorphisms in Iranian Patients With Juvenile Idiopathic Arthritis.

Acta Med Iran 2017 Nov;55(11):676-682

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. AND Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous cluster of complex diseases, in which both the genetic and environmental factors seem to play a role in the development of the disease. The current study aims to assess the association of programmed cell death 1 (PDCD1, also called PD-1) gene variants with JIA vulnerability in Iranian population. In this case-control association study, we investigated a group of 50 Iranian patients with JIA in comparison with 202 healthy controls and evaluated the frequency of alleles, genotypes, and haplotypes of PDCD1 single-nucleotide polymorphisms (SNPs), comprising PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T, using PCR-RFLP method. Both the allelic and genotype frequencies of PD-1.1, PD-1.3 and PD-1.9 were similar in two groups of patients and controls. Moreover, no significant difference was observed between the two groups of patients and controls for GGC (PD-1.1 G, PD-1.3 G, PD-1.9 C), GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C), and AGT (PD-1.1 A, PD-1.3 G, PD-1.9 T) haplotypes. Our results did not show any association between PDCD1 SNPs and the development of JIA in Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2017

Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23.

Mod Rheumatol 2017 Sep 15;27(5):862-867. Epub 2016 Dec 15.

a Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Objective: Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23.

Methods: Peripheral blood monocyte isolated from 10 HLA-B27 patients and five HLA-B27 normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR.

Results: RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not significant.

Conclusions: Our data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27. UPR appears to be associated with overproduction of IL-23 in AS macrophages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14397595.2016.1259716DOI Listing
September 2017

Identification, Isolation, and Functional Assay of Regulatory T Cells.

Immunol Invest 2016 Oct 15;45(7):584-602. Epub 2016 Jul 15.

a Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Two categories of regulatory T cells (Tregs), nTreg and iTreg, play vital roles in orchestrating the integrity of a host in the course of an immune response. Tregs commonly belong to CD4+ CD25+ T cells and they are characterized by a transcription factor - forkhead box P3 (FoxP3). Within the space of the last few years, interests have been drawn to Tregs as a therapeutic tool in several settings like autoimmune disease, transplantation, and tumor disorders. As a consequence, to assess the functional properties of Tregs, namely through their ability to suppress other cells, cytokine expression, and proliferation in a variety of conditions, it is mandatory to gain better approaches to this end. This would be beneficial in designing better-than-ever therapeutic methods with regard to Tregs properties. Gaining better insights into the underlying mechanisms of immune regulation, by means of straightforward and less time-consuming techniques, will hopefully permit the therapeutic application of these cells in the control of human disorders. This review aims at going through the basic methods for Treg isolation as well the efficiency of the commonly exerted in vitro assays of Tregs-mediated immune suppression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2016.1193869DOI Listing
October 2016

PDCD1 single nucleotide genes polymorphisms confer susceptibility to juvenile-onset systemic lupus erythematosus.

Autoimmunity 2015 25;48(7):488-93. Epub 2015 Jun 25.

b Department of Immunology , School of Medicine, Tehran University of Medical Sciences , Tehran , Iran .

Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease in which both the genetic and environmental factors seem to be involved in the etiopathogenesis of the disease. The aim of this study was to evaluate the association of programmed cell death 1 (PDCD1, also called PD-1) gene polymorphisms with JSLE susceptibility in Iranian population. In this case-control association study, three PDCD1 SNPs, including PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T were genotyped in 50 Iranian patients with JSLE and 202 healthy unrelated controls, using PCR-RFLP method. The PD-1.1 A allele was found to be more frequent in the case group compared with controls (6% vs. 1.5%, p = 0.024). Moreover, the GG genotype was less frequent in cases than in controls (88% vs. 97%, p = 0.021). The other PDCD1 SNPs did not show association. At the haplotypic level, no significant differences was recognized between the two groups of case and control neither for the GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C) nor for the GGC haplotype (PD-1.1 G, PD-1.3 G, PD-1.9 C). Our findings support the influence of the PD1.1 A SNP on the development of JSLE in Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/08916934.2015.1058370DOI Listing
August 2016

Impacts of anti-EGFR monoclonal antibody in prostate cancer PC3 cells.

Hum Antibodies 2010 ;19(2-3):63-70

Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Epidermal growth factor receptor (EGFR) network appears to be a rich target for prostate cancer. Thus, in this current investigation, to pursue our newly developed anti-EGFR monoclonal antibody (mAb) in prostate cancer, its inhibitory effect was investigated in PC3 cells. The binding specificity of antibody was examined by flow cytometry and immunofluorescence staining. The cultivated cells were treated with various doses of the anti-EGFR mAb at different time points and the cellular and/or molecular impacts were assessed. MTT assay was utilized to examine the cytotoxic effects. Semi-quantitative RT-PCR was used to evaluate the expression of EGFR and some important apoptosis signaling molecules (e.g., MAPK-1, STAT-5, Akt-1 kinase). Flow cytometric and immunofluorescence staining analyses showed that the anti-EGFR mAb can bind to EGFR with high specificity. The results revealed that the anti-EGFR mAb can inhibit cell growth in a dose and time dependent manner. RT-PCR analysis revealed that the binding of anti-EGFR mAb to its receptors can eventually result in downregulation of Akt-1 kinase gene, but not MAPK-1, STAT-5 and EGFR genes. Based on our findings, it can be concluded that Akt-1 is the most important downstream signaling molecules affected by anti-EGFR mAbs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/HAB-2010-0229DOI Listing
January 2011