INVOLVEMENT OF REACTIVE OXYGEN INTERMEDIATES IN CYCLOOXYGENASE-2 EXPRESSION INDUCED BY INTERLEUKIN-1, TUMOR-NECROSIS-FACTOR-ALPHA, AND LIPOPOLYSACCHARIDE

被引:385
作者
FENG, L
XIA, YY
GARCIA, GE
HWANG, D
WILSON, CB
机构
[1] Scripps Res Inst, DEPT IMMUNOL IMM5, LA JOLLA, CA 92037 USA
[2] LOUISIANA STATE UNIV, PENNINGTON BIOMED RES CTR, BATON ROUGE, LA 70808 USA
关键词
REACTIVE OXYGEN INTERMEDIATES; NADPH; MESANGIAL CELL; PTPASE; KC;
D O I
10.1172/JCI117842
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Reactive oxygen intermediates (ROIs) play an important role in inflammatory processes as mediators of injury and potentially in signal transduction leading to gene expression. Cyclooxygenase (COX) is a rate-limiting enzyme in prostanoid biosynthesis, and its recently cloned inducible form, COX-2, is induced by proinflammatory cytokines, This study linked ROIs to the signaling pathways that induce COX-2 expression, The hydroxyl radical scavengers DMSO (1%), as well as di- and tetramethylthiourea, inhibited IL-1-, TNF alpha-, and LPS-induced COX-2 expression in rat mesangial cells, The suppression of COX-2 mRNA expression correlated with the COX-2 protein level, In comparison with the prolonged induction of the inducible gene encoding protein-tyrosine phosphatase by hydrogen peroxide, the COX-2 gene was only transiently induced, Protein-tyrosine phosphatase is also induced by heat shock and chemical stress, whereas COX-2 is not, Superoxide was a more potent inducer for COX-2 than hydrogen peroxide, In addition, NADPH stimulated COX-2 expression, and an inhibitor of NADPH oxidase blocked COX-2 expression induced by TNF alpha. COX-2 and KC gene expression costimulated by IL-1 were inhibited differentially by the scavengers, These studies demonstrate that oxidant stress is a specific and important inducer of COX-2 gene expression, This induction may contribute to the deleterious amplification of prostanoids in inflammation and compound the direct effects of ROI production,
引用
收藏
页码:1669 / 1675
页数:7
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