Cyclo-oxygenase-2 regulates inducible ICAM-1 and VCAM-1 expression in human vascular smooth muscle cells.
Prostaglandins are well characterised inflammatory mediators, whose formation is regulated by constitutive (COX-1) or inducible (COX-2) isoforms of cyclo-oxygenase. We have previously demonstrated that IL-1 beta causes an induction of COX-2 in human vascular smooth muscle (1). This present study investigates the ability of different cytokines to induce ICAM-1 and VCAM-1 on human vascular smooth muscle, and tests whether co-induced COX-2 would regulate their expression. IL-1 beta induced ICAM-1, and COX activity, while it had no affect on VCAM-1. Conversely, IL-4 induced VCAM-1, while it had no effect on PGE2 release or ICAM-1 expression. Inhibition of IL-1 beta induced COX-2 and elevated ICAM-1 expression, an effect reversed by exogenous PGE2. Furthermore, IL-1 beta inhibited IL-4 induced VCAM-1 expression, which was also reversed by COX-2 inhibition. These results demonstrate that COX-2 limits adhesion molecule expression on human vascular smooth muscle cells and suggest that COX-2 can play a protective role in cardiovascular and inflammatory diseases.
Department of Applied Pharmacology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom. Bishop@sun.uchc.edu
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Burke-Gaffney
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Hellewell
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Mitchell
D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases