INTRACELLULAR CA2-OXIDE MEDIATED ENHANCEMENT OF INTERLEUKIN-8 SECRETION IN HUMAN ENDOTHELIAL-CELLS( DEPENDENCE OF NITRIC)

Nitric oxide (NO.) can induce transient [Ca2+] changes in endothelial cells not different from receptor mediated signalling, Whether this Ca 2+ signal may provide a link with IL-8 secretion induced by NO. donors was investigated in human endothelial cells. Sodium nitroprusside (SN P) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) dose dependently inc reased IL-8 production in this cell type. Additive IL-8 secretion was found with TNF alpha. Buffering intracellular Ca2+ with MAPT/AM suppre ssed NO. induced [Ca2+](i) changes and reduced subsequent IL-8 secreti on. The additive effect of both NO. donors on TNF alpha induced IL-8 s ecretion was completely blocked in the presence of MAPT/AM. SKF 96365, which has been shown to block receptor mediated Ca2+ entry, and TMB-8 , which blocks intracellular Ca2+ release, both inhibited IL-8 secreti on, particularly when TNF alpha was used as a costimulator, indicating that [Ca2+](i) changes are important components of IL-8 induction by NO.. (C) 1997 Federation of European Biochemical Societies.