title: Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen-induced arthritis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Inflammatory Diseases, Monash University, Clayton, Victoria, Australia.
authors.forename: Yuan H
authors.initials: YH
authors.lastname: Yang
authors.forename: Eric F
authors.initials: EF
authors.lastname: Morand
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Getting
authors.forename: Mark
authors.initials: M
authors.lastname: Paul-Clark
authors.forename: Dong L
authors.initials: DL
authors.lastname: Liu
authors.forename: Simon
authors.initials: S
authors.lastname: Yona
authors.forename: Robert
authors.initials: R
authors.lastname: Hannon
authors.forename: Julia C
authors.initials: JC
authors.lastname: Buckingham
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Flower
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000172:deficiency / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003907:Dexamethasone