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

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

<P> 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 &#12557;g/ml) increased the leukocyte proliferation and nitric oxide(NO) generation, which were measured as [<SUP>3</SUP>H]-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<SUB>50</SUB> around 50nM. The addition of anti-lipocortin 1(Anti-LC1) reversed dexamethasone effects: 0.24, 1.2, 6 &#12557;g/ml of Anti-LC1 reversed dexamethasone(50 nM)-induced suppression of thymidine uptake by 9&#8273;3%, 16&#8273;3%, 36&#8273;5%, respectively; 0.24, 1.2, and 6 &#12557;g/ml of Anti-LC1 reversed dexamethasone-induced decrease of nitrite concentration by 49&#8273;16%, 61&#8273;20%, 77&#8273;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.