INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR POTENTIATE ANGIOTENSIN-II-STIMULATED, AND CALCIUM IONOPHORE-STIMULATED PROSTAGLANDIN-E2 SYNTHESIS IN RAT RENAL MESANGIAL CELLS

In resting mesangial cells, angiotensin II and the calcium ionophore A23187 stimulated prostaglandin E2 (PGE2) formation. After pretreatment with interleukin 1β (IL-1β) or tumor necrosis factor α (TNFα), which are themselves potent stimuli for PGE2 synthesis, mesangial cells displayed an amplified response to angiotensin II and A23187. The cytokine-induced effects occurred in a time- and dose-dependent manner and were attenuated by actinomycin D, cycloheximide and dexamethasone. IL-1β and TNFα treatment also increased the amount of arachidonic acid released after stimulation of cells with angiotensin II and A23187. In addition, IL-1β but not TNFα treatment augmented the formation of PGE2 from exogenous arachidonic acid by mesangial cells. Furthermore, the conversion of prostaglandin H2 to PGE2 was not changed by IL-1β and TNFα. These results suggest that IL-1β and TNFα exert a priming effect on PGE2 production in mesangial cells. © 1990.