Modulation of Inflammation and Response to Dexamethasone by Annexin 1 in Antigen-Induced Arthritis

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

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.

Original languageAmerican English
Pages (from-to)976-984
Number of pages9
JournalArthritis and Rheumatism
Volume50
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

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