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.
|Titolo:||An oligomer targeted against protein kinase C alpha prevents interleukin-1 alpha induction of cyclooxygenase expression in human endothelial cells|
MAIER, JEANETTE ANNE MARIE (Primo)
|Parole Chiave:||Protein Biosynthesis; Prostaglandin-Endoperoxide Synthases; Humans; DNA, Antisense; Oligonucleotides; Endothelium, Vascular; Inflammation; Base Sequence; Interleukin-1; Cells, Cultured; Cytoplasm; Cell Membrane; Molecular Sequence Data; Enzyme Induction; Protein Kinase C; Phorbol Esters|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||mar-1993|
|Digital Object Identifier (DOI):||10.1006/excr.1993.1057|
|Appare nelle tipologie:||01 - Articolo su periodico|