INTERLEUKIN-2 MODULATES THE RESPONSIVENESS TO ANGIOTENSIN-II IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS

Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, en hanced the increase in intracellular Ca2+ ([Ca2+](i)) induced by angio tensin II (AII) in vascular smooth muscle cells (VSMC). IL-2 itself di d not affect the basal [Ca2+](i) level or the maximal response of [Ca2 +](i) increase induced by AII. Furthermore, IL-2-induced enhancement w as not observed in the absence of extracellular Ca2+, suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the stimu lation of DNA synthesis induced by All, although IL-2 alone did not st imulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kin ases, significantly inhibited IL-2-induced enhancement of both Ca2+ in flux and DNA synthesis induced by AII. A neutralizing antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) p artially inhibited IL-l-induced enhancement of DNA synthesis induced b y All. These findings suggest that autocrine KB-EGF is partially invol ved in the mechanism of IL-2-induced enhancement of DNA synthesis. On the other hand IL-2 stimulated both glycosaminoglycan (GAG) and prosta cyclin syntheses and enhanced the stimulation of both GAG and prostacy clin syntheses induced by AII. Therefore, IL-2 may play important role s in the pathogenesis of atherosclerosis and vascular disease by modul ating the responsiveness to AII in VSMC. (C) 1997 Elsevier Science Ire land Ltd.