Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen-induced arthritis.
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.
Yang
Yuan H
YH
Centre for Inflammatory Diseases, Monash University, Clayton, Victoria, Australia.
Morand
Eric F
EF
Getting
Stephen J
SJ
Paul-Clark
Mark
M
Liu
Dong L
DL
Yona
Simon
S
Hannon
Robert
R
Buckingham
Julia C
JC
Perretti
Mauro
M
Flower
Roderick J
RJ
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
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003907:Dexamethasone