Production of nitric oxide and its regulation in murine peritoneal macrophages treated with cisplatin and lipopolysaccharide

Abstract

Murine peritoneal macrophages treated with cisplatin or lipopolysaccharide (LPS) showed an enhanced production of nitric oxide (NO) and increased tumoricidal activity against P815 mastocytoma cells. The NO secretion and generation of macrophage-mediated tumoricidal activity were significantly inhibited by L-N-monomethyl arginine (LNMMA), a specific inhibitor of L-arginine pathway. Induction of NO production in macrophages on activation with cisplatin or LPS is inhibited by EGTA, nifedipine, TMB-8 and W-7, suggesting the probable involvement of Ca2+ and calmodulin in the induction of NO release. Protein kinase C and tyrosine kinase inhibitors significantly inhibited the cisplatin/LPS induced NO production, suggesting that phosphorylation via these kinases may up-regulate the NO synthase activity in macrophages.