Cyclooxygenase-2 expression in macrophages:: Modulation by protein kinase C-α

被引：96

作者：

Giroux, M ^{[1
]}

Descoteaux, A ^{[1
]}

机构：

[1] Univ Quebec, Inst Armand Frappier, INSERM, Laval, PQ H7V 1B7, Canada

来源：

JOURNAL OF IMMUNOLOGY | 2000年 / 165卷 / 07期

关键词：

D O I：

10.4049/jimmunol.165.7.3985

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for high levels of PG production during inflammation and immune responses. Previous studies with pharmacological inhibitors suggested a role for protein kinase C (PKC) in PG production possibly by regulating COX-2 expression. In this study, we addressed the role of PKC-alpha in the modulation of COX-2 expression and PGE(2) synthesis by the overexpressing of a dominant-negative (DN) mutant of this isoenzyme in the mouse macrophage cell line RAW 264.7. We investigated the effect of various stimuli on COX-2 expression, namely, LPS, IFN-gamma, and the intracellular parasite Leishmania donovani, Whereas LPS-induced COX-2 mRNA and protein expression were down-regulated in DN PKC-alpha-overexpressing clones, IFN-gamma-induced COX-2 expression was up-regulated in DN PKC-alpha-overexpressing clones with respect to normal RAW 264.7 cells. Measurements of PGE, levels revealed a strong correlation between PGE(2) secretion and IFN-gamma-induced COX-2 mRNA and protein levels in DN PKC-alpha-overexpressing clones. Taken together, these results suggest a role for PKC-alpha in the modulation of LPS- and IFN-gamma-induced COX-2 expression, as well as in IFN-gamma-induced PGE(2) secretion.

引用

页码：3985 / 3991

页数：7

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