Lipocortin 1 mediates the suppressive effects of dexamethasone on CoNinduced proliferative response and nitric oxide production in rat splenic leukocytes

ABSTRACT

Lipocortin 1 has been proposed as a putative mediator of anti-inflammatory actions of glucocorticoids. We investigated the role of lipocortin 1 in the effect of dexamethasone using rat splenic leukocytes. Concanavalin A(ConA; 1-microgram/ml) increased the leukocyte proliferation and nitric oxide(NO) generation, which were measured as (3H)-thymidine uptake by the cells and nitrite accumulation in the culture media, respectively. Dexamethasone suppressed CoNinduced cell proliferation, in a concentration-dependent manner with EC-50 around 50nM. The addition of anti-lipocortin 1 (Anti-LC1) reversed dexamethasone effects 0.24, 1.2, 6 microgram/ml of Anti-LC1 reversed dexamethasone(50nM)-induced suppression of thymidine uptake by 9+/-3%, 16+/-3%, 36+/-5%, respectively; 0.24, 1.2, and 6-microgram/ml of Anti-LC1 reversed dexamethasone-induced decrease of nitrite concentration by 49 +/- 16%, 61 +/- 20%, 77 +/- 19 %, respectively. The present data indicate that lipocortin 1 mediates, at least in part, glucocorticoids-induced suppression of leukocyte proliferation and blockade of NO generation.