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

Tu Rapp Hoang, André Hammermüller, Eilhard Mix, Hans Jürgen Kreutzer, Roland Goerlich, Hansjürgen Köhler, Horst Nizze, Hans Jürgen Thiesen, Saleh M. Ibrahim

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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 destruction is crucial, the potential activating effect of Fas on mouse fibroblast cell line NIH3T3 was investigated. On treatment with anti-Fas in vitro, the cell death of NIH3T3 fibroblasts was reduced and the expression of proinflammatory cytokines TNF-alpha and IL-6 was increased. These findings suggest that impairment of immune tolerance by increased T-cell reactivity does not lead to enhanced susceptibility to CIA and point to a role of Fas in joint destruction.

Original languageBritish English
Pages (from-to)R404-414
JournalArthritis Research and Therapy
Volume6
Issue number5
StatePublished - 2004

Fingerprint

Dive into the research topics of 'A proinflammatory role for Fas in joints of mice with collagen-induced arthritis.'. Together they form a unique fingerprint.

Cite this