A proinflammatory role for Fas in joints of mice with collagen-induced arthritis

Arthritis Research & Therapy
Hoang Tu-RappSaleh Ibrahim

Abstract

Collagen-induced arthritis (CIA) is a chronic inflammatory disease bearing all the hallmarks of rheumatoid arthritis, e.g. polyarthritis, synovitis, and subsequent cartilage/bone erosions. One feature of the disease contributing to joint damage is synovial hyperplasia. The factors responsible for the hyperplasia are unknown; however, an imbalance between rates of cell proliferation and cell death (apoptosis) has been suggested. To evaluate the role of a major pathway of cell death - Fas (CD95)/FasL - in the pathogenesis of CIA, DBA/1J mice with a mutation of the Fas gene (lpr) were generated. The susceptibility of the mutant DBA-lpr/lpr mice to arthritis induced by collagen type II was evaluated. Contrary to expectations, the DBA-lpr/lpr mice developed significantly milder disease than the control littermates. The incidence of disease was also significantly lower in the lpr/lpr mice than in the controls (40% versus 81%; P < 0.05). However DBA-lpr/lpr mice mounted a robust immune response to collagen, and the expression of local proinflammatory cytokines such as, e.g., tumor necrosis factor alpha (TNF-alpha) and IL-6 were increased at the onset of disease. Since the contribution of synovial fibroblasts to inflammation and joint ...Continue Reading

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Citations

Jul 3, 2007·Pediatric Rheumatology Online Journal·Karoline EhlertJosef Vormoor
Jul 1, 2005·Arthritis Research & Therapy·Kristin BauerSaleh M Ibrahim
Dec 20, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Stanford L Peng
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Feb 3, 2016·The Journal of Rheumatology·Eun-Jin HanWan-Uk Kim
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Sep 15, 2005·Rheumatology·S L Peng
Jan 5, 2021·Current Opinion in Rheumatology·Hao Li, George C Tsokos

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Methods Mentioned

BETA
PCR
ELISA

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