Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen-induced arthritis

✍ Scribed by Yuan H. Yang; Eric F. Morand; Stephen J. Getting; Mark Paul-Clark; Dong L. Liu; Simon Yona; Robert Hannon; Julia C. Buckingham; Mauro Perretti; Roderick J. Flower

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 353 KB
• Volume: 50
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.20201

✦ Synopsis

Abstract

Objective

Annexin 1 (Anx‐1) is a putative mediator of the antiinflammatory actions of glucocorticoids (GCs). This study investigated the role of Anx‐1 in experimental arthritis and in GC‐mediated inhibition of inflammation, using antigen‐induced arthritis (AIA) in Anx‐1 knockout (Anx‐1^−/−^) mice.

Methods

Arthritis was induced by intraarticular injection of methylated BSA (mBSA) in mice preimmunized with mBSA. Disease was assessed after 7 days by histologic examination of the knee joints. Serum levels of anti‐mBSA IgG were determined by enzyme‐linked immunosorbent assay. Cytokine messenger RNA (mRNA) expression was detected by real‐time polymerase chain reaction.

Results

A significant exacerbation of arthritis was observed in the Anx‐1^−/−^ mice compared with wild‐type (WT) mice. This was associated with increased mRNA expression of synovial interleukin‐1β, tumor necrosis factor α, interleukin‐6, and macrophage migration inhibitory factor. Dexamethasone significantly reduced the histologic severity of synovitis and bone damage in the WT mice, but exerted no inhibitory effects in the Anx‐1^−/−^ mice, and also significantly reduced the serum levels of anti‐mBSA IgG and the numbers of peripheral blood neutrophils and lymphocytes in WT mice, but had no such effect in Anx‐1^−/−^ mice.

Conclusion

Anx‐1 exerts endogenous antiinflammatory effects on AIA via the regulation of cytokine gene expression, and also mediates the antiinflammatory actions of dexamethasone in AIA.