Lipocortin 1 Mediates the Suppressive Effects of Dexamethasone on ConA-induced Proliferative Response and Nitric Oxide Production in Rat Splenic Leukocytes

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 ${\mu}g/ml$) 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 ConA-induced cell proliferation, in a concentration-dependent manner with $EC_{50}$ around 50nM. The addition of anti-lipocortin l(Anti-LCl) reversed dexamethasone effects: 0.24, 1.2, 6 ${\mu}g/ml$ of Anti-LC1 reversed dexamethasone(50 nM)-induced suppression of thymidine uptake by $9{\pm}3%$, $16{\pm}3%$, $36{\pm}5%$, respectively; 0.24, 1.2, and 6 ${\mu}g/ml$ of Anti-LCI reversed dexa-methasone-induced decrease of nitrite concentration by $49{\pm}16%$, $61{\pm}20%$, $77{\pm}19%$, respectively. The present data indicate that lipocortin 1 mediates, at least in part, glucocorticoids-induced suppression of leukocyte proliferation and blockade of NO generation.