Lee Juliette L, Mukhtar Hasan, Bickers David R, Kopelovich Levy, Athar Mohammad
Departments of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Toxicol Appl Pharmacol. 2003 Nov 1;192(3):294-306. doi: 10.1016/s0041-008x(03)00301-6.
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.
环氧化酶（COX），一种前列腺素内过氧化物合酶（PTGS），催化花生四烯酸转化为前列腺素。前列腺素是脂质信号介质，在广泛多样的生理和病理生理过程中发挥核心作用，包括炎症、生殖、伤害感受和胃肠道保护。抑制环氧化酶活性是非甾体抗炎药（NSAIDs）发挥其镇痛、解热、抗炎和抗血栓作用的机制。目前认为COX存在三种同工型。在本综述中，我们简要介绍了COX在皮肤药理学和毒理学中的作用，包括其在正常生理、皮肤炎症、伤害感受、伤口愈合和肿瘤发生中的作用。COX依赖途径影响角质形成细胞分化、毛囊发育和毛发生长。还讨论了COX-2在皮肤病理生理学中的关键作用。COX-2介导皮肤炎症过程，包括炎症性痛觉过敏和伤害感受，给予特定的COX-2抑制剂可减轻水肿、血管通透性和皮肤炎症的其他指标。在动物模型和人类中的多项研究表明，COX-2抑制剂具有癌症化学预防特性。选择性COX-2抑制剂具有更有利的副作用谱。COX-2抑制剂的局部制剂正在被开发为治疗COX-2介导的皮肤病的一种新型药理学方法。
