title: siRNA-mediated knock-down of COX-2 in melanocytes suppresses melanogenesis.
abstract: Cyclooxygenase-2 (COX-2) is an enzyme induced in response to multiple mitogenic and inflammatory stimuli, including UV light. UV-induced COX-2 expression induces production of prostaglandin E2 (PGE2) in keratinocytes, which mediates inflammation and cell proliferation. Until recently, studies regarding COX-2 and PGE2 in the skin have focused on keratinocytes and skin cancer and the effect of PGs produced by keratinocytes on melanocytes. However, the effects of COX-2 itself or COX-2 inhibitors on melanogenesis are not well known. Therefore, to establish the role of COX-2 in melanogenesis, we investigated the effects of knock-down of COX-2 in melanocytes on melanin production and the expression of melanogenic molecules through silencing of COX-2 expression with COX-2 short interfering RNA (siRNA). COX-2 knock-down in melanocytes decreased the expressions of tyrosinase, TRP-1, TRP-2, gp100 and MITF and also reduced tyrosinase enzyme activity. Furthermore, COX-2 siRNA-transfected melanocytes showed markedly reduced alpha-melanocyte stimulating hormone (α-MSH)-induced melanin production. In addition, α-MSH-induced COX-2 expression in both scrambled siRNA-transfected and COX-2 siRNA-transfected melanocytes was greater than α-MSH-untreated cells. Our results suggest that COX-2 might be a candidate target for the development of anti-melanogenic agents and α-MSH-induced pigmentation could be closely associated with COX-2 expression. COX-2 inhibitors might therefore be of particular use in whitening cosmetics for hyperpigmentation disorders such as melasma, postinflammatory hyperpigmentation and solar lentigo.
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji Y
authors.initials: JY
authors.lastname: Kim
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Shin
authors.forename: Miri R
authors.initials: MR
authors.lastname: Kim
authors.forename: Seung-Kyung
authors.initials: SK
authors.lastname: Hann
authors.forename: Sang H
authors.initials: SH
authors.lastname: Oh
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D017495:Hyperpigmentation / Q000188:drug therapy; D007370:Interferon Type I / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000201:enzymology* / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009336:Necrosis; D011257:Pregnancy Proteins / Q000378:metabolism; D034741:RNA, Small Interfering; D014162:Transfection; D000521:alpha-MSH; D058951:gp100 Melanoma Antigen / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007370:Interferon Type I; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D011257:Pregnancy Proteins; D034741:RNA, Small Interfering; D058951:gp100 Melanoma Antigen; C020947:interferon tau; D000521:alpha-MSH; D014442:Monophenol Monooxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D015232:Dinoprostone