Cyclooxygenases in the skin: pharmacological and toxicological implications.
Cyclooxygenase (COX), a prostaglandin-endoperoxide synthase (PTGS), catalyzes the formation of prostaglandins from arachidonic acid. Prostaglandins are lipid signaling mediators that play a central role in a broad range of diverse physiological and pathophysiological processes, including inflammation, reproduction, nocioception, and gastrointestinal protection. Inhibition of cyclooxygenase activity is the mechanism by which nonsteroidal antiinflammatory drugs (NSAIDS) exert their analgesic, antipyretic, antiinflammatory, and antithrombotic effects. COX is currently believed to exist in three isoforms. In this review, we provide a concise state-of-the-art description of the role of COX in pharmacology and toxicology of skin including its involvement in normal physiology, cutaneous inflammation, nociception, wound healing, and tumorigenesis. COX-dependent pathways influence keratinocyte differentiation, hair follicle development, and hair growth. The critical role of COX-2 in pathophysiology of skin is also addressed. COX-2 mediates inflammatory processes in skin, including inflammatory hyperalgesia and nociception, and administration of specific COX-2 inhibitors reduces edema, vascular permeability, and other markers of cutaneous inflammation. A number of studies in animal models and in humans show that COX-2 inhibitors possess cancer chemopreventive properties. Selective COX-2 inhibitors have a more favorable side-effect profile. Topical formulations of COX-2 inhibitors are being developed as a novel pharmacologic approach for the treatment of COX-2 mediated skin diseases.
Lee
Juliette L
JL
Departments of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Mukhtar
Hasan
H
Bickers
David R
DR
Kopelovich
Levy
L
Athar
Mohammad
M
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D006801:Humans; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases / Q000145:classification / Q000378:metabolism*; D012867:Skin / Q000187:drug effects* / Q000201:enzymology*
D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases