scholarly journals Gender Differences in Rheumatoid Arthritis: Interleukin-4 Plays an Important Role

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Chaojie Yu ◽  
Chong Liu ◽  
Jie Jiang ◽  
Hao Li ◽  
Jiarui Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gender Differences ◽  
Cell Differentiation ◽  
Clinical Manifestations ◽  
Cell Receptor ◽  
Chronic Inflammatory Disease ◽  
Interleukin 4 ◽  
Receptor Interaction ◽  
Hub Genes ◽  
Kegg Pathways

Introduction. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical peripheral polyarthritis. A large number of studies have shown that RA is characterized by gender differences in clinical manifestations. The purpose of this study is to identify the key molecules of gender differences in patients with RA and to provide new molecular targets for personalized therapy. Material and Methods. The data from GSE55457 were downloaded from the comprehensive gene expression comprehensive database, and two groups (RA vs. No-RA groups, Male-RA vs. Female-RA groups) of differentially expressed genes (EDGs) were obtained by GEO2R. The GO function and KEGG pathway analyses of DEGs were carried out through the plug-in ClueGO in Cytoscape. Based on the STRING online, a protein-protein interaction (PPI) network was constructed. Hub genes were selected from CytoHubba. Through the intersection of the top 10 hub genes in two sets of EDGs, the key genes and related KEGG pathways were found. Quantitative Real-Time PCR and Western blotting analysis were performed for verification. Results. 1230 DEGs were screened between RA and No-RA groups, and 306 DEGs were screened between male and female RA groups. The common key gene of the two groups is IL-4. Between RA group and No-RA group, interleukin-4 (IL-4) participates in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, etc. Conclusion. This study contributes to the molecular biological mechanism of gender differences in RA. IL-4 may have played an important role.

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4550-4556 ◽  
Author(s):  
Frederique Ponchel ◽  
Ann W. Morgan ◽  
Sarah J. Bingham ◽  
Mark Quinn ◽  
Maya Buch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Large Population ◽  
Chronic Inflammatory Disease ◽  
T Cell Differentiation ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells

Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4+ T cells than healthy controls. Furthermore, a smaller proportion of these cells contains a T-cell receptor excision circle (TREC). Patients with RA also have unusual populations of T cells. These include immature cells characterized as CD45RBbrightCD45RA+CD62L− by flow cytometry and a large population that coexpresses CD45RA and CD45RO. These cells are hyperresponsive to mitogen and TCR stimulation when compared to naive cells. Additionally, an unusual putative central memory subset expressing CD62L, but not CD45RA, appears in RA patients at the expense of more typical cells. Levels of C-reactive protein correlate inversely with the TREC content of naive T cells and positively with the sizes of naive and immature atypical T-cell subsets. These data suggest that inflammation drives proliferation of naive T cells in RA and encourages their differentiation into atypical, hyperresponsive progeny. TREC content of individual naive and atypical T-cell subsets suggests an ontogeny consistent with this hypothesis. These studies provide further evidence of a T-cell differentiation defect in RA, which could explain some of the well-characterized immunologic features of the disease.

scholarly journals Bioinformatics Analysis to Identify Key Genes and Pathways Associated with Sex Differences in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Siwei Su ◽  
Wenjun Jiang ◽  
Xiaoying Wang ◽  
Sen Du ◽  
Lu Zhou ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Kegg Pathways ◽  
Ppi Networks ◽  
Males And Females ◽  
Key Genes

Abstract ObjectiveThis study aims to explore the key genes and investigated the different signaling pathways of rheumatoid arthritis (RA) between males and females.Data and MethodsThe gene expression data of GSE55457, GSE55584, and GSE12021 were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software. Then, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein interaction (PPI) networks of DEGs were constructed by Cytoscape 3.6.0. ResultsA total of 416 upregulated DEGs and 336 downregulated DEGs were identified in males, and 744 upregulated DEGs and 309 downregulated DEGs were identified in females.IL6, MYC, EGFR, FOS and JUN were considered as hub genes in RA pathogenesis in males, while IL6, ALB, PTPRC, CXCL8 and CCR5 were considered as hub genes in RA pathogenesis in females. ConclusionIdentified DEG may be involved in the different mechanisms of RA disease progression between males and females, and they are treated as prognostic markers or therapeutic targets for males and females. The pathogenesis mechanism of RA is sex-dependent.

scholarly journals The Identified Hub Gene GlcN in Osteoarthritis Progression and Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jingsheng Liu ◽  
Xiaoli Dong ◽  
Yining Liu ◽  
Kai Wang ◽  
Shuanhu Lei ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Point Of View ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Hub Genes ◽  
Data Set ◽  
Treatment Groups ◽  
R Language ◽  
Kegg Pathways ◽  
Osteoarthritis Progression

Background. As a chronic disease, osteoarthritis has caused great trouble to the health of middle-aged and elderly people. Studies have shown that glucosamine (GlcN) can be used to abate the progression and improve this disease. Based on this point of view, we try to verify the connection between GlcN and osteoarthritis and find more effective biomarkers. Methods. We downloaded the GSE72575 data set from the GEO database, and used the R language to perform DEG analysis on the gene expression profile of the samples. Next, the GO function and the KEGG signaling pathways were analyzed through the DAVID database, and then, the KEGG pathways enriched in the gene set were analyzed based on GSEA. Then, the PPI network of DEGs was constructed based on the STRING online database, and finally, the hub genes were selected by Cytoscape. Results. Three GlcN-treated MH7A cell treatment groups and 3 control groups in the GSE72575 data set were studied. Through analysis, there were 52 DEGs in these samples. Then, through GO, KEGG, and GSEA, regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway, FoxO signaling pathway, JAK-STAT signaling pathway, PI3K-Akt signaling pathway, TGF-beta signaling pathway, and ECM receptor interaction were involved in the regulatory mechanisms of the osteoarthritis pathogenesis. After that, the hub genes IL6 and DDIT3 were identified through PPI network construction and analysis. And it was found that IL6 was lowly expressed in the group with GlcN-treated MH7A cells, while DDIT3 was highly expressed. Conclusion. The above results provide a basis for GlcN to participate in the treatment of osteoarthritis and a possibility for finding effective therapeutic targets.

scholarly journals MAPK10 Expression as a Prognostic Marker of the Immunosuppressive Tumor Microenvironment in Human Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Huahui Li ◽  
Yuting Li ◽  
Ying Zhang ◽  
Binbin Tan ◽  
Tuxiong Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Transmembrane Protein ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Mapk Signaling ◽  
Receptor Interaction ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Pathway Analyses

Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients. HCC patients with low MAPK10 expression have lower expression scores of tumor infiltration lymphocytes (TILs) and stromal cells in the TME and increased scores of tumor cells than those with high MAPK10 expression. Further transcriptomic analyses revealed that the immune activity in the TME of HCC was markedly reduced in the low-MAPK10 group of HCC patients compared to the high-MAPK10 group. Additionally, we identified 495 differentially expressed immune-associated genes (DIGs), with 482 genes down-regulated and 13 genes up-regulated in parallel with the decrease of MAPK10 expression. GO enrichment and KEGG pathway analyses indicated that the biological functions of these DIGs included cell chemotaxis, leukocyte migration and positive regulation of the response to cytokine–cytokine receptor interaction, T cell receptor activation and MAPK signaling pathway. Protein–protein interaction (PPI) analyses of the 495 DIGs revealed five potential downstream hub genes of MAPK10, including SYK, CBL, VAV1, LCK, and CD3G. Several hub genes such as SYK, LCK, and VAV1 could respond to the immunological costimulatory signaling mediated by the transmembrane protein ICAM1, which was identified as a down-regulated DIG associated with low-MAPK10 expression. Moreover, ectopic overexpression or knock-down of MAPK10 could up-regulate or down-regulate ICAM1 expression via phosphorylation of c-jun at Ser63 in HCC cell lines, respectively. Collectively, our results demonstrated that MAPK10 down-regulation likely contributes to the immunosuppressive TME of HCC, and this gene might serve as a potential immunotherapeutic target and a prognostic factor for HCC patients.

With an antibody whose duty's double, a step towards ending asthma trouble?

2013 ◽  
Vol 451 (2) ◽  
pp. e1-e3
Author(s):  
Eric J. Sundberg
Keyword(s):  
Inflammatory Responses ◽  
Molecular Mimicry ◽  
Cell Signalling ◽  
Chronic Inflammatory Disease ◽  
Interleukin 4 ◽  
Receptor Interaction ◽  
Inflammatory Cascade ◽  
Treatment And Prevention ◽  
Il Interleukin

Asthma is a debilitating chronic inflammatory disease of the airways that results in shortness of breath, wheezing and coughing, often triggered by inhalation of common allergens. The prevalence and severity of asthma has increased dramatically over the last several decades to the point where several hundred million people worldwide are affected and each year tens of thousands of individuals die prematurely from asthma symptoms. The rise in disease prevalence is particularly evident in the developed world, where childhood exposure to bacteria and viruses has decreased dramatically, while the use of antibiotics, especially early in life, and births by Caesarean section have increased significantly; correlations that support the hygiene hypothesis. Central to the pathogenesis of asthma are the roles of TH2-type cytokines, including IL (interleukin)-4, IL-5, IL-9 and IL-13, in stimulating and perpetuating an inflammatory cascade that drives detrimental changes in airway structure and function. IL-4 and IL-13, in particular, have been targets of therapeutic development because, together, they specifically promote nearly all of the clinical features of asthma. Their inflammatory functions are highly complementary, but not identical, in large part because they share cell-surface receptors and transcription factors through which they stimulate cell signalling. In this issue of the Biochemical Journal, Redpath et al. have taken advantage of the shared receptor nature of the IL-4- and IL-13-mediated inflammatory responses to generate a novel antibody to the third ectodomain (D3) of IL-13Rα1 (IL-13 receptor α1), which forms a requisite binding site for both interleukins. This antibody potently neutralizes both IL-4 and IL-13 activities in vitro. Using X-ray crystallography complemented by molecular interaction and functional analyses, they clearly define its mechanism of dual cytokine neutralization as one of molecular mimicry of the interleukin–receptor interaction. Considering the complexity of the cytokine-mediated inflammatory cascade that defines asthma pathogenesis, such therapeutics that can effectively and simultaneously neutralize the actions of multiple cytokines and may play a significantly expanded role in the treatment and prevention of asthma in the future.

Gender differences in cardiovascular risk of patients with rheumatoid arthritis

QJM ◽  
2019 ◽  
Vol 112 (9) ◽  
pp. 657-661
Author(s):  
M Adawi ◽  
B Gurovich ◽  
S Firas ◽  
A Watad ◽  
N l Bragazzi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gender Differences ◽  
Cardiovascular Risk ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Chronic Inflammatory Disease ◽  
Cardiac Events ◽  
Brachial Artery Diameter ◽  
Artery Disease ◽  
A Prospective Study

Abstract Background Rheumatoid Arthritis (RA) is a chronic inflammatory disease, affecting women more than men, with a more aggressive course in women. Design A prospective study that recruited 58 patients (46 women aged 56 ± 12 years) with active long-standing RA disease (>12 months). Our goals were to measure their endothelial function, part of the cardiovascular risk assessment. Methods The Brachial Artery method measured endothelial function (the flow mediated percent change [FMD percentage] of the brachial artery diameter). A senior Rheumatologist clinically evaluated all subjects. Mann Whitney rank sum test estimated gender differences among the RA patients. Results Median FMD% change for men was −6.07%, while median FMD% change for women was 0.44% (Z = 2.38, P = 0.01). Baseline Brachial artery diameter was larger in men (Z = 2.52, P = 0.01); however, tender joints count and BMI were greater in women (Z=−2.24, P = 0.01; Z=−3.99, P = 0.001), respectively. Conclusions Women with RA have significantly better endothelial function than men with RA. It means that even though RA is 3-fold more prevalent in women, women are more protected from atherosclerotic coronary artery disease and cardiac events.

Novel Nano Carriers for the Treatment of Progressive Auto Immune Disease Rheumatoid Arthritis

2020 ◽  
Vol 26 ◽  
Author(s):  
Ritu Mishra ◽  
Swati Gupta
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Autoimmune Disease ◽  
Drug Delivery Systems ◽  
Clinical Manifestations ◽  
Adaptive Immune Response ◽  
Delivery Systems ◽  
Current Therapy ◽  
Genetic And Environmental Factors ◽  
Novel Drug

Background: Rheumatoid arthritis (RA) is the most common occurring progressive, autoimmune disease, affecting 1% of the population and the ratio of affected women is three times as compared to men in most developing countries. Clinical manifestations of RA are the presence of anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) in blood, tendered joints and soreness of the muscles. Some other factors which may lead to chronic inflammation are genetic and environmental factors as well as adaptive immune response. Several conventional drugs are available for the treatment of RA but have their own drawbacks which can be overcome by the use of novel drug delivery systems. : The objective of the present review is to focus on the molecular pathogenesis of the disease and its current conventional treatment with special reference to the role of novel drug delivery systems encapsulating anti rheumatic drugs and herbal drugs in passive and receptor mediated active targeting against RA. On reviewing the conventional and current therapeutics agains RA, we conclude that, although the current therapy for the treatment of RA is capable enough, yet more advances in the field of targeted drug delivery will sanguinely result in effective and appropriate treatment of this autoimmune disease.

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