[Effects of six naphthalenesulfonamide derivatives on LPS-induced release of tumor necrosis factor from mouse...

The effects of six naphthalenesulfonamide derivatives were studied on the LPS-induced release of tumor necrosis factor (TNF) from mouse peritoneal macrophages primed with A23187. The calmodulin (CaM) antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives N-(6-aminobutyl)-5-chloro-1-naphthalenesulfonamide and N-(6-aminoethyl)-5-chloro-1-naphthalenesulfonamide (10-400 ng/ml) were found to inhibit LPS-induced TNF release in a dose-dependent manner, and the protein kinase C (PKC) activator, N-(n-heptyl)-5-chloro-1-naphthalenesulfonamide (SC-10) and its two derivatives, N-(n-quinyl)-5-chloro-1-naphthalenesulfonamide and N-(n-butyl)-5-chloro-1-naphthalenesulfonamide (1-16 micrograms/ml) were shown to increase LPS-induced TNF release at suboptimal doses in a dose-dependent manner. These results suggest that the LPS-induced release of TNF is CaM-dependent and PKC may play an important role in this process.