Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide.

Abstract

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-, TNFa-, 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 TNFa. 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. (J. CUi Invest. 1995. 95:1669-1675.) Key words: reactive oxygen intermediates * NADPH * mesangial cell -

Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice

“…The WD increased COX2 and angptl2 expression, two markers of inflammation, in CAT mice only. We previously reported that COX2 expression correlated with the level of damage in endothelial cells isolated from coronary artery disease patients [75], while others showed that oxidative stress stimulated COX2 expression [21]. In addition, we reported that 9 months of CAT magnified 50-folds the rise in COX2 expression associated with aging in the mouse aorta [26].…”

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Isochaihulactone protects PC12 cell against H2O2 induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model

“…Reactive oxygen species themselves can increase and/or induce cellular cyclooxygenase-2 (COX-2) expression [8][9][10] . In addition, apoptotic cell death induced by exposure to cyanide can be inhibited by selective COX-2 inhibition [11,12] .…”