The Role of Lipocortin-1 in the Corticosteroid Action in Collagen Induced Arthritis

Choi, Seung Won; Yoo, Bin; Kim, Mi Jung; Moon, Hee Bom

Abstract

OBJECTIVES
Lipocortin-1 (LC-1), a member of annexin family of calcium-binding proteins induced by corticosteroid, originally evoked interest as one of the secondary messengers in the antiinflammatory action of corticosteroid, But the exact mechanism of LC-1 responsible for antiinflammatory effect is still unclear. We investigated the potential role of LC-1 in the effect of corticosteroid on amelioration of collagen induced arthritis (CIA) in mice.
METHODS
Four groups of DBA/1j mice were immunized by intradermal injection of 5mg/kg of type 2 collagen with complete Freunds adjuvant which was boostered on day 21 and 42. Group 1 received no treatment and group 2 received 1mg/kg dexamethasone intraperitoneally twice weekly from day 21. Group 3 and 4 were treated with 50 and 0.5microgram/kg of anti LC-1 monoclonal antibody subcutaneously and dexamethasone from day 21 twice weekly, respectively. The prevalence of arthritis and arthritis score were assessed twice weekly. At week 10, we measured serum anticollagen antibody levels and splenic mononuclear cell stimulation indices (SI) to collagen. RESULT: CIA started to develop after 4 weeks of collagen treatment in all groups. All mice of group 1 developed arthritis by the 9 week. Treatment with dexamethasone markedly inhibited arthritis development (P<0.05). Cotreatment of anti LC-1 monoclonal antibody and dexamethasone abolished the antiinflammatory effect of dexamethasone (P<0.05). But there was no significant difference in the serum levels of anticollagen antibody or splenic mononuclear cell SI among the groups.
CONCLUSION
These findings support the hypothesis that LC-1 is involved, at least in part, in the antiinflammatory actions of corticosteroid in chronic inflammation, although the mechanism of which is unclear.