regulation of cox-2 expression in fibroblasts, osteoblasts, mast cells, and Macrophages

摘要

The prostaglandin synthase/cyclooxygenase (COX) enzymes catalyze two reactions. The cyclooxy genase activity of these enzymes first converts free arachidonic acid, released from membrane lipids by a phospholipase, to PGG_2. This intermediate is then converted to PGH_2 by the COX hydroperoxidase activity. PGH_2 is the precursor for all prostanoids-prostaglandins, thromboxanes and prostacyclins.Cyclooxygenase activity is present in nearly all cells. For many years the rate-limiting step in prostanoid production in response to cell stimulation was thought to be activation of phospholipase(s) to release membrane-bound arachidonic acid. Prostaglandin production was thought to be limited by arachidonic acid availability; constitutive levels of COX were thought to be present in excess in cells, and available to convert free arachidonic acid to PGH_2. It was assumed that only one COX gene is present in mammalian genomes. However, studies of glucocorticoid inhibition of prostaglandin production [1], antigenic isoforms of COX [2], and identification of an inducible mRNA that cross-hybridized with "COX" cDNA [3] suggested a second, inducible COX gene might exist.