title: Cyclooxygenase enzymes as targets for therapeutic intervention in inflammation.
abstract: The synthesis of bioactive prostanoids is controlled, in part, by the action of the cyclooxygenase (COX; prostaglandin H synthase; prostaglandin endoperoxidase) family of enzymes. Inhibition of these enzymes underlies the therapeutic action of the nonsteroidal antiinflammatory drugs (NSAIDs) and also leads to the adverse side effects, such as gastrointestinal ulceration, associated with these drugs. Interest in the therapeutic targeting of this system as a means of controlling inflammation was further expanded by the demonstration in the early 1990s of the existence of a second, inducible, isoform of COX, COX-2. Originally, it was believed that this isoform was expressed at sites of inflammation but not in noninflamed tissue, where a constitutively expressed isoform, COX-1, was thought to be responsible for the physiological production of eicosanoid mediators. This presented the opportunity to develop novel "super aspirins," which could selectively inhibit the inducible isoform, exert potently antiinflammatory effects and, importantly, be largely devoid of the deleterious side effects of conventional NSAIDs. However, it is now being increasingly accepted that COX-2 is also expressed in chronic inflammatory diseases and is seen during the resolution of inflammatory reactions and in areas undergoing wound healing. Inhibition of this isoform in these situations has revealed potential, previously hidden, pitfalls associated with COX-2 inhibition. This article examines the roles of the COX enzymes in inflammation, with emphasis on the emerging role of COX-2 during inflammatory resolution, as well as discussion of some future directions for antiinflammatory therapy that this research has suggested.
authors.affiliation: Department of Experimental Pathology, William Harvey Research Institute, St. Bartholomew's & Royal London Hospitals School of Medicine & Dentistry, Charterhouse Square, London, UK.
authors.forename: P R
authors.initials: PR
authors.lastname: Colville-Nash
authors.forename: D W
authors.initials: DW
authors.lastname: Gilroy