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

Arthritis Rheum. 2004 Mar;50(3):976-84. doi: 10.1002/art.20201.

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-1 beta, tumor necrosis factor alpha, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A1 / deficiency
  • Annexin A1 / metabolism*
  • Anti-Inflammatory Agents / pharmacology*
  • Antibody Formation
  • Arthritis, Experimental / blood
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology*
  • Arthritis, Experimental / physiopathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dexamethasone / pharmacology*
  • Gene Expression / drug effects
  • Leukocytes / drug effects
  • Mice
  • Mice, Knockout
  • Synovial Membrane / metabolism

Substances

  • Annexin A1
  • Anti-Inflammatory Agents
  • Cytokines
  • Dexamethasone