retinaldehyde and 1-oleoyl-2-acetylglycerol

We investigated the role of protein kinase C (PK-C) in the activation of cytotoxic peritoneal murine macrophages (M phi) by IFN-gamma or by IFN-beta. Two potent inhibitors of PK-C, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and retinal, were used. We found that both drugs inhibited in a dose-dependent manner the activation of cytotoxicity induced by IFN-beta, suggesting the requirement for intact PK-C activity in this process. In contrast, neither H-7 nor retinal inhibited the activation of cytotoxic M phi by IFN-gamma, indicating that IFN-gamma acts through a PK-C-independent pathway. The effectiveness of both drugs in inhibiting PK-C in intact M phi was evaluated by measuring the inhibition of induction of c-fos mRNA by L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol, a process that has been shown to be dependent on PK-C activation. We have found a strict correlation in the dose-dependent inhibition by both drugs of c-fos mRNA induction and activation of M phi by IFN-beta. These results indicate that different pathways of activation are triggered by IFN-gamma and IFN-beta, the former being independent from and the latter dependent on intact PK-C activity.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Cytotoxicity, Immunologic; Diglycerides; Interferon Type I; Interferon-gamma; Isoquinolines; Macrophage Activation; Macrophages; Male; Mice; Mice, Inbred C57BL; Piperazines; Protein Kinase C; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fos; Retinaldehyde; Retinoids

1-Oleoyl-2-acetyl-glycerol which activates Ca2+-activated phospholipid-dependent protein kinase, induced the superoxide-production of human neutrophils, while other diacylglycerols did not. The induction was independent of extracellular calcium and did not accompany the increase of the intracellular free calcium. The superoxide-release by the diacylglycerol was inhibited by retinal, the inhibitor of the protein kinase. The diacylglycerol stimulated the phosphorylation of at least 4 proteins in intact neutrophils, the phosphorylation of which was stimulated by phorbol 12-myristate 13-acetate, the activator of the protein kinase. These observations indicate the possible involvement of the kinase in the induction process.

Topics: Diglycerides; Enzyme Activation; Glycerides; Humans; Kinetics; Neutrophils; Oleic Acid; Oleic Acids; Phosphoproteins; Phosphorylation; Protein Kinase C; Protein Kinase Inhibitors; Protein Kinases; Retinaldehyde; Superoxides; Tetradecanoylphorbol Acetate