Prostaglandins and inflammation: the cyclooxygenase controversy.
Prostaglandins (PGs) are arachidonic acid metabolites produced by the action of the enzyme cyclooxygenase (COX). Although PGs are important mediators of inflammation in various diseases, they also are key factors in the physiological regulation of gastrointestinal and renal homeostasis. The finding that two distinct COX isoforms are responsible for PG synthesis has provided basis to the opposite actions of PGs in inflammation and homeostasis regulation. COX-1-derived PGs are thought to mediate cytoprotective actions on the gastrointestinal mucosa, whereas COX-2-derived PGs are assumed to display pro-inflammatory properties. This dichotomy has led to the development of selective inhibitors of COX-2 activity which are safer for the gastrointestinal mucosa than the classic inhibitors of both COX isoforms. However, some COX-2 anti-inflammatory properties have been recently demonstrated in several experimental models of inflammation. These studies have raised some concern about the potential adverse effects of COX-2 selective inhibitors. In addition, there is evidence that COX-1 displays pro-inflammatory properties, depending on the organ and on the stage of the inflammatory response. This review will focus on the roles of COX-1 and COX-2 in inflammation, based on studies involving pharmacologic COX inhibitors as well as COX knock-out mice, with a particular emphasis on the gastrointestinal tract.
Morteau
O
O
Department of Pulmonary Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. morteau_0@a1.tch.harvard.edu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D004064:Digestive System / Q000187:drug effects / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases