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

被引：95

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

共 48 条

[11]

DESCOTEAUX A, 1990, J IMMUNOL, V145, P846

[12] Cyclooxygenase in biology and disease [J].

Dubois, RN ;

Abramson, SB ;

Crofford, L ;

Gupta, RA ;

Simon, LS ;

Van De Putte, LBA ;

Lipsky, PE .

FASEB JOURNAL, 1998, 12 (12) :1063-1073

[13] SEQUENCE OF HUMAN PROTEIN KINASE-C-ALPHA [J].

FINKENZELLER, G ;

MARME, D ;

HUG, H .

NUCLEIC ACIDS RESEARCH, 1990, 18 (08) :2183-2183

[14]

FLETCHER BS, 1992, J BIOL CHEM, V267, P4338

[15] ALPHA-INTERFERON-INDUCED TRANSCRIPTION OF HLA AND METALLOTHIONEIN GENES CONTAINING HOMOLOGOUS UPSTREAM SEQUENCES [J].

FRIEDMAN, RL ;

STARK, GR .

NATURE, 1985, 314 (6012) :637-639

[16] SELECTIVE-INHIBITION OF NS-398 ON PROSTANOID PRODUCTION IN INFLAMED TISSUE IN RAT CARRAGEENAN-AIR-POUCH INFLAMMATION [J].

FUTAKI, N ;

ARAI, I ;

HAMASAKA, Y ;

TAKAHASHI, S ;

HIGUCHI, S ;

OTOMO, S .

JOURNAL OF PHARMACY AND PHARMACOLOGY, 1993, 45 (08) :753-755

[17] Engagement of tumor necrosis factor mRNA by an endotoxin-inducible cytoplasmic protein [J].

Gueydan, C ;

Houzet, L ;

Marchant, A ;

Sels, A ;

Huez, G ;

Kruys, V .

MOLECULAR MEDICINE, 1996, 2 (04) :479-488

[18]

Habib A, 1997, J IMMUNOL, V158, P3845

[19] Characterization of the RNA binding proteins forming complexes with a novel putative regulatory region in the 3′-UTR of TNF-α mRNA [J].

Hel, Z ;

Di Marco, S ;

Radzioch, D .

NUCLEIC ACIDS RESEARCH, 1998, 26 (11) :2803-2812

[20] HUMAN CYCLOOXYGENASE-2 CDNA [J].

HLA, T ;

NEILSON, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (16) :7384-7388

← 1 2 3 4 5 →