[Inhibitory effects of protein kinase C inhibitor and calmodulin antagonist on tumor necrosis factor production by mouse macrophages].
Mouse peritoneal macrophages were primed with calcium ionophore calcimycin 1 mumol.L-1 for 8 h and then elicited by lipopolysaccharides (LPS, 10 ng.ml-1) for 6 h to induce tumor necrosis factor (TNF), measured by crystal violet staining assay using murine fibroblast L929 cells. Protein kinase C (PKC) inhibitor, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) and calmodulin (CaM) antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) were studied on LPS-induced TNF production by macrophages. Addition of H-7 (0.31-50 micrograms.ml-1) and W-7 (10-4000 ng.ml-1) simultaneously with LPS to the culture medium suppressed LPS-induced TNF production in a concentration-dependent manner. When macrophages were pretreated with W-7 (10 ng.ml-1), LPS-induced TNF production was completely inhibited at 8 h. These results suggest that TNF production by macrophages may be dependent on the PKC and CaM.
Tian
M
M
Research Laboratory of Natural and Synthetic Drugs, School of Pharmacy, Second Military Medical University, Shanghai, China.
Zhang
J P
JP
Qian
D H
DH
Li
G C
GC
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D002147:Calmodulin; D007546:Isoquinolines; D008070:Lipopolysaccharides; D010879:Piperazines; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C