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.
An oligomer targeted against protein kinase C alpha prevents interleukin-1 alpha induction of cyclooxygenase expression in human endothelial cells / J. A. Maier, G. Ragnotti. - In: EXPERIMENTAL CELL RESEARCH. - ISSN 0014-4827. - 205:1(1993 Mar), pp. 52-58. [10.1006/excr.1993.1057]
An oligomer targeted against protein kinase C alpha prevents interleukin-1 alpha induction of cyclooxygenase expression in human endothelial cells
J.A. MaierPrimo
;
1993
Abstract
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.Pubblicazioni consigliate
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