Studies on the induction of lipocortin-1 by glucocorticoids

Abstract

Part of the anti-inflammatory efficacy of glucocorticoids has been ascribed to the inhibition of eicosanoid formation which is brought about by lipocortins (LC, phospholipase A2 inhibitory proteins) whose synthesis is induced by corticosteroids. We have investigated the effect of glucocorticoids on eicosanoid formation and lipocortin-1 induction in a human cell line in vitro and in patients with inflammatory lung disease in vivo. Human promyelocitic U-937 cell line was differentiated by 24 h incubation with phorbol myristate acetate (PMA, 6 ng/ml), then dexamethasone (1 microM) was added for further 16 h. In these conditions the steroid treatment caused both the release of lipocortin-1 in the cellular supernatant and the inhibition of eicosanoid release. These results suggest that the responsiveness of these cells to steroids is dependent on the phase of cell activation-differentiation. The selective release of the lipocortin-1 may explain the inhibition of eicosanoid formation. Patients with inflammatory lung disease underwent glucocorticoid treatment at clinically effective doses. LC-1 expression was significantly stimulated in alveolar macrophages, but not in blood-derived lympho-monocytes. These results suggest that also in vivo cell responsiveness to glucocorticoids is acquired during cell differentiation from blood monocyte to tissue macrophage.