An oligomer targeted against protein kinase C alpha prevents interleukin-1 alpha induction of cyclooxygenase expression in human endothelial cells.
We have previously demonstrated that interleukin-1 alpha (IL-1), a potent polypeptide mediator of immune and inflammatory responses, induces the expression of cyclooxygenase (cox) in human endothelial cells. The mechanism by which binding of IL-1 to its receptor stimulates gene expression remains unclear. Since phorbol 12-myristate 13-acetate, which directly binds and activates protein kinase C (PKC), induced cox expression, we examined the role of PKC as an intracellular mediator of IL-1 activity in human endothelial cells. IL-1 induced the translocation of PKC from the cytosol to the membrane. H7, a selective inhibitor of PKC, as well as an antisense oligomer blocking PKC alpha translation suppressed IL-1 induction of cox mRNA. These findings establish that PKC plays a role in the signal transduction pathway leading to the induction of cox in human endothelial cells.
Maier
J A
JA
Dipartimento di Scienze Biomediche e Biotecnologie, Sezione di Patologia Generale, Brescia, Italy.
Ragnotti
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G
D001483:Base Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D016373:DNA, Antisense / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D014176:Protein Biosynthesis / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*
D016373:DNA, Antisense; D007375:Interleukin-1; D009841:Oligonucleotides; D010703:Phorbol Esters; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C