Distinct roles for the NF-kappa B1 (p50) and c-Rel transcription factors in inflammatory arthritis
- Author(s)
- Campbell, IK; Gerondakis, S; O'Donnell, K; Wicks, IP;
- Details
- Publication Year 2000-06,Volume 105,Issue #12,Page 1799-1806
- Journal Title
- JOURNAL OF CLINICAL INVESTIGATION
- Publication Type
- Journal Article
- Abstract
- Rheumatoid arthritis (RA) is a complex disease, with contributions from systemic autoimmunity and local inflammation. Persistent synovial joint inflammation and invasive synovial pannus tissue lead to joint destruction. RA is characterized by the production of inflammatory mediators, many of which are regulated by the Rel/NF-kappa B transcription factors. Although an attractive target for therapeutic intervention in inflammatory diseases, Rel/NF-kappa B is involved in normal physiology, thus global inhibition could be harmful. An alternate approach is to identify and target the Rel/NF-kappa B subunits critical for components of disease. To assess this, mice with null mutations in c-rel or nfkb1 were used to examine directly the roles of c-Rel and p50 in models of acute and chronic inflammatory arthritis. We found c-Rel-deficient mice were resistant to collagen-induced arthritis but had a normal response in an acute, destructive arthritis model (methylated BSA/IL-1 induced arthritis) suggesting c-Rel is required for systemic but not local joint disease. In contrast, p50-deficient mice were refractory to induction of both the chronic and acute arthritis models, showing this subunit is essential for local joint inflammation and destruction. Our data suggest Rel/NF-kappa B subunits pray distinct roles in the pathogenesis of inflammatory arthritis and may provide a rationale for more specific therapeutic blockade of Rel/NF-kappa B in RA.
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Keywords
- NF-KAPPA-B; COLLAGEN-INDUCED ARTHRITIS; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; MICE LACKING; II COLLAGEN; T-CELLS; RHEUMATOID SYNOVIUM; TARGETED DISRUPTION; DENDRITIC CELLS
- Publisher's Version
- https://doi.org/10.1172/JCI8298
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-06-01 12:00:00