18. Anandamide attenuates the inflammatory phenotype of rheumatoid arthritis synovial fibroblasts by activating multiple receptor pathways

2012 ◽  
Vol 26 ◽  
pp. S5-S6
Author(s):  
T. Lowin ◽  
A. Gräber ◽  
E. Neumann ◽  
R.H. Straub
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Inflammatory Phenotype ◽  
Multiple Receptor

scholarly journals Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in Rheumatoid Arthritis

2020 ◽  
Author(s):  
Yilin Wang ◽  
Aneesah Khan ◽  
Aristotelis Antonopoulos ◽  
Laura Bouché ◽  
Christopher D Buckley ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Cells ◽  
Joint Destruction ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Surface Proteins ◽  
Cellular Interactions ◽  
Inflammatory Microenvironment ◽  
Distinct Disease ◽  
Inflammatory Phenotype

AbstractIn healthy joints, synovial fibroblasts (SFs) provide the microenvironment required to mediate homeostasis but are recognized to adopt a pathological role in rheumatoid arthritis (RA), promoting the infiltration and activation of immune cells to perpetuate local inflammation, pain and joint destruction. Carbohydrates (glycans) attached to cell surface proteins are fundamental regulators of cellular interactions between stromal and immune cells, but very little is known about the glycome of SFs or how glycosylation regulates their biology. Here we fill these gaps in our understanding of stromal guided pathophysiology by systematically mapping glycosylation pathways in healthy and arthritic SFs. We used a combination of transcriptomic and glycomic analysis to show that transformation of fibroblasts into pro-inflammatory cells in RA is associated with profound glycan remodeling, a process that involves reduction of α2-6 terminal sialylation that is mostly mediated by TNFα-dependent inhibition of the glycosyltransferase ST6Gal1. We also show that sialylation of SFs correlates with distinct disease stages and SFs functional subsets in both human RA and models of mouse arthritis. We propose that pro-inflammatory cytokines in the joint remodel the SF-glycome, transforming a regulatory tissue intended to preserve local homeostasis, into an under-sialylated and highly pro-inflammatory microenvironment that contributes to an amplificatory inflammatory network that perpetuates chronic inflammation. These results highlight the importance of cell glycosylation in stromal immunology.

scholarly journals Senescent synovial fibroblasts accumulate prematurely in rheumatoid arthritis tissues and display an enhanced inflammatory phenotype

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Manuel J. Del Rey ◽  
Álvaro Valín ◽  
Alicia Usategui ◽  
Sandra Ergueta ◽  
Eduardo Martín ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Mrna Expression ◽  
Inflammatory Mediators ◽  
Synovial Fibroblasts ◽  
Initial Exposure ◽  
Inflammatory Phenotype ◽  
Expression Response ◽  
Synovial Tissues ◽  
Proteins Secretion

Abstract Background Accumulation of senescent cells has been associated with pro-inflammatory effects with deleterious consequences in different human diseases. The purpose of this study was to analyze cell senescence in human synovial tissues (ST), and its impact on the pro-inflammatory function of synovial fibroblasts (SF). Results The expression of the senescence marker p16INK4a (p16) was analyzed by immunohistochemistry in rheumatoid arthritis (RA), osteoarthritis (OA), and normal ST from variably aged donors. The proportion of p16(+) senescent cells in normal ST from older donors was higher than from younger ones. Although older RA and OA ST showed proportions of senescent cells similar to older normal ST, senescence was increased in younger RA ST compared to age-matched normal ST. The percentage of senescent SA-β-gal(+) SF after 14 days in culture positively correlated with donor’s age. Initial exposure to H2O2 or TNFα enhanced SF senescence and increased mRNA expression of IL6, CXCL8, CCL2 and MMP3 and proteins secretion. Senescent SF show a heightened IL6, CXCL8 and MMP3 mRNA and IL-6 and IL-8 protein expression response upon further challenge with TNFα. Treatment of senescent SF with the senolytic drug fenofibrate normalized IL6, CXCL8 and CCL2 mRNA expression. Conclusions Accumulation of senescent cells in ST increases in normal aging and prematurely in RA patients. Senescence of cultured SF is accelerated upon exposure to TNFα or oxidative stress and may contribute to the pathogenesis of synovitis by increasing the production of pro-inflammatory mediators.

scholarly journals TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-κB signaling

2017 ◽  
Vol 15 (7) ◽  
pp. 685-696 ◽  
Author(s):  
Lin Wang ◽  
Hongyan Dong ◽  
Guanhua Song ◽  
Rui Zhang ◽  
Jihong Pan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Inflammatory Phenotype

The Role of Synovial Fibroblasts in Mediating Joint Destruction in Rheumatoid Arthritis

2005 ◽  
Vol 11 (5) ◽  
pp. 563-568 ◽  
Author(s):  
Ingmar Meinecke ◽  
Edita Rutkauskaite ◽  
Steffen Gay ◽  
Thomas Pap
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Synovial Fibroblasts

FRI0020 BMP-2 and TGF-B Inhibit IL-34 Expression in Rheumatoid Arthritis Synovial Fibroblasts

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 432.3-433
Author(s):  
M. Chemel-Mary ◽  
B. Legoff ◽  
Y. Maugars ◽  
D. Heymann ◽  
F. Verrechia
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts

Notch‐1 and Notch‐3 Mediates Hypoxia‐Induced Synovial Fibroblasts Activation in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Jianhai Chen ◽  
Wenxiang Cheng ◽  
Jian Li ◽  
Yan Wang ◽  
Jingqin Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Notch 1 ◽  
Notch 3

scholarly journals MiR-140-3p inhibits the cell viability and promotes apoptosis of synovial fibroblasts in rheumatoid arthritis through targeting sirtuin 3

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Beibei Zu ◽  
Lin Liu ◽  
Jingya Wang ◽  
Meirong Li ◽  
Junxia Yang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Pearson Correlation ◽  
Fibrous Tissue ◽  
Synovial Fibroblasts ◽  
Cell Counting ◽  
Sirtuin 3 ◽  
Fibrous Tissues

Abstract Background Synovial fibroblasts (SFs) with the abnormal expressions of miRNAs are the key regulator in rheumatoid arthritis (RA). Low-expressed miR-140-3p was found in RA tissues. Therefore, we attempted to investigate the effect of miR-140-3p on SFs of RA. Methods RA and normal synovial fibrous tissue were gathered. The targets of miR-140-3p were found by bioinformatics and luciferase analysis. Correlation between the expressions of miR-140-3p with sirtuin 3 (SIRT3) was analyzed by Pearson correlation analysis. After transfection, cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry. The expressions of miR-140-3p, SIRT3, Ki67, Bcl-2, Bax, and cleaved Caspase-3 were detected by RT-qPCR or western blot. Results Low expression of miR-140-3p and high expression of SIRT3 were found in RA synovial fibrous tissues. SIRT3 was a target of miR-140-3p. SIRT3 expression was negatively correlated to the expression of miR-140-3p. MiR-140-3p mimic inhibited the MH7A cell viability and the expressions of SIRT3, Ki67, and Bcl-2 and promoted the cell apoptosis and the expressions of Bax and cleaved Caspase-3; miR-140-3p inhibitor showed an opposite effect to miR-140-3p mimic on MH7A cells. SIRT3 overexpression not only promoted the cell viability and inhibited cell apoptosis of MH7A cells but also reversed the effect of miR-140-3p mimic had on MH7A cells. Conclusions The results in this study revealed that miR-140-3p could inhibit cell viability and promote apoptosis of SFs in RA through targeting SIRT3.

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