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The Journal of Immunology, 2000, 165: 3985-3991.
Copyright © 2000 by The American Association of Immunologists

Cyclooxygenase-2 Expression in Macrophages: Modulation by Protein Kinase C-{alpha}1

Mélanie Giroux and Albert Descoteaux2

Institut National de la Recherche Scientifique-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada

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 PGE2 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 PGE2 levels revealed a strong correlation between PGE2 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 PGE2 secretion.




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