COX-2: a pivotal enzyme in mucosal protection and resolution of inflammation.
The discovery of a second form of cyclooxygenase, COX-2, led to a burst of research aimed at the development of nonsteroidal anti-inflammatory drugs that would not damage the gastrointestinal tract. In the years since, this promise has only been partially fulfilled. Selective COX-2 inhibitors cause less gastric damage than conventional, nonselective COX inhibitors, but their use is still associated with significant gastrointestinal injury, and with toxicity in the renal and cardiovascular systems. COX-2 is now recognized as a source of mediators that produce many beneficial and detrimental effects in the digestive system. In this review, the roles of COX-2 in mucosal defense and injury are discussed. Furthermore, contributions of COX-2-derived products to the long-term consequences of intestinal inflammation, including cancer, are reviewed.
Wallace
John L
JL
Inflammation Research Network, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. wallacej@ucalgary.ca
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D003092:Colitis / Q000150:complications / Q000188:drug therapy / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000209:etiology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D044045:Lipoxins / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D044045:Lipoxins; D051546:Cyclooxygenase 2