BETA-ADRENERGIC REGULATION OF RENIN EXPRESSION IN DIFFERENTIATED U-937 MONOCYTIC CELLS

Previous studies from our laboratories demonstrated that human decidua l macrophages and peripheral mononuclear cells express renin. In the p resent study, we found that U-937 monocytes, induced to differentiate into macrophage-like cells by treatment with phorbol dibutyrate (PDBU) , express renin mRNA and release renin (95% of which is in the form of prorenin). Treatment of these PDBU-exposed cells with dibutyryl-cAMP (1 mM) caused a 20-fold increase in renin mRNA and a 10-fold increase in prorenin release. Forskolin (10 mu M), an activator of adenylyl cyc lase, and terbutaline (100 mu M), a beta(2)-adrenergic agonist known t o increase cAMP levels, also increased renin mRNA and prorenin release . The secretory response to terbutaline was potentiated by the type IV cyclic AMP-phosphodiesterase (PDE) inhibitor Ro 20-1724 (50 mu M). An giotensin II agonist inhibited the stimulatory effect of terbutaline o n renin secretion as did the cytokines tumor necrosis factor-alpha and lipopolysaccharide plus interferon-gamma. Since other studies have sh own that U-937 cells possess beta(2)-adrenergic receptors and express mainly the type IV PDE, the present findings strongly suggest that bet a-adrenergic receptors in mononuclear cells are coupled to renin expre ssion via the cAMP transduction pathway. The results support a possibl e role for the renin-angiotensin system in macrophage function and sug gest potential autocrine regulatory mechanisms in prorenin expression. (C) 1997 Elsevier Science Inc.