We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Fas ligation on macrophages enhances IL-1R1-Toll-like receptor 4 signaling and promotes chronic inflammation.
- Authors
Ma, Yingyu; Liu, Hongtao; Tu-Rapp, Hoang; Thiesen, Hans-Juergen; Ibrahim, Saleh M; Cole, Shawn M; Pope, Richard M
- Abstract
The nonapoptotic functions of Fas ligation are incompletely characterized. In contrast to expectations, we show here that Fas-deficient mice developed less-severe collagen-induced arthritis than did control mice. Despite having milder arthritis, Fas-deficient mice had more of the critical pro-inflammatory mediator interleukin-1 beta (IL-1 beta) in their joints, suggesting inefficient activation through IL-1 receptor 1 (IL-1R1) when Fas signaling is deficient. In primary human macrophages and macrophages from Fas- or Fas ligand (FasL)-deficient mice, interruption of Fas-FasL signaling suppressed nuclear factor-kappa B activation and cytokine expression induced by IL-1 beta and lipopolysaccharide. This cross-talk was mediated by the Fas-associated death domain through interaction with myeloid differentiation factor 88. These observations document a unique mechanism whereby Fas-FasL interactions enhance activation through the IL-1R1 or Toll-like receptor 4 pathway, which may contribute to the pathogenesis of chronic arthritis.
- Publication
Nature immunology, 2004, Vol 5, Issue 4, p380
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1054