INTERFERON-GAMMA INCREASES CELLULAR CALCIUM-ION CONCENTRATION AND INOSITOL 1,4,5-TRISPHOSPHATE FORMATION IN HUMAN RENAL-CARCINOMA CELLS - RELATION TO ICAM-1 ANTIGEN EXPRESSION

In the present study, we investigated the effect of inteferon-gamma (IFN-gamma) on cellular calcium ion concentration [Ca2+](i) and inositol 1,4,5-trisphosphate (Ins 1,4,5-P-3) formation in the human renal carcinoma cell line CaKi-1. We also examined the possible role of a Ca2+-dependent mechanism during IFN-gamma-induced intercellular adhesion molecule 1 (ICAM-1) antigen expression. IFN-gamma caused a rapid concentration-dependent rise in [Ca2+](i), which was partly inhibited by diltiazem, a calcium channel blocker, TMB-8, an inhibitor of intracellular calcium redistribution, and in calcium-free medium. IFN-gamma caused a fourfold increase in Ins 1,4,5-P, formation. The induction of ICAM-1 antigen expression was synergistically enhanced by 4-bromocalcium ionophore A23187. Finally, the calcium antagonists diltiazem, TMB-8 and EGTA, as well as two potent inhibitors of Ca2+-dependent kinases, calmidazolium (R24571) and W7, had no or only a minor inhibitory effect on IFN-gamma induction. Our data suggest that IFN-gamma increases [Ca2+](i) in CaKi-1 cells by stimulating influx of Ca2+ and release of Ca2+ from intracellular stores, probably via Ins 1,4,5-P, formation. IFN-gamma signal transduction in our model may not be limited to an increase in [Ca2+]i and Ins 1,4,5-P,, since IFN-gamma-induced ICAM-1 antigen expression was abrogated to a minor degree by calcium antagonists and not coupled to Ins 1,4,5-P, formation.