INTERLEUKIN-1-BETA INDUCES THE EXPRESSION OF AN ISOFORM OF NITRIC-OXIDE SYNTHASE IN INSULIN-PRODUCING CELLS, WHICH IS SIMILAR TO THAT OBSERVED IN ACTIVATED MACROPHAGES

The suppressive and cytotoxic effects of interleukin-1-beta (IL-1-beta) on rodent insulin-producing cells observed in vitro are probably mediated through formation of nitric oxide (NO). In this study we demonstrate that IL-1-induced NO formation in isolated rat islets and insulin-producing HIT cells is more sensitive to inhibition by N(G)-monomethyl-L-arginine than to inhibition by N(G)-nitro-L-arginine, thus suggesting that IL-1-exposed insulin-producing cells express an isoform of nitric oxide synthase similar to that present in activated macrophages. Furthermore, IL-1-beta markedly increased the mRNA levels of the inducible macrophage form of nitric oxide synthase in HIT cells.