title: Possible involvement of enhanced prostaglandin E2 production in the photosensitivity in xeroderma pigmentosum group A model mice.
abstract: Xeroderma pigmentosum group A (XPA) gene-deficient mice cannot repair UV-induced DNA damage and easily develop skin cancers by UV irradiation. Therefore, XPA-deficient mice are a useful model of human XP and represent a promising tool for photobiologic studies of the disorder. Exposure to ultraviolet (UV) B (280-320 nm) radiation greatly enhanced inflammation and immunosuppression in these mice. To investigate the molecular mechanisms of enhanced UV inflammation and immunosuppression, we determined the amount of prostaglandin (PG) E2, an inflammatory mediator and immunomodulator, and analysed the expression of cyclooxygenase (COX) mRNA in the ear skin of XPA-deficient mice after UV irradiation. In XPA-deficient mice, the amount of PGE2 significantly increased at 48 and 72 h after UVB irradiation to the level that was 8- and 16-fold higher than those in wild-type mice, respectively. The expression level of COX-2 mRNA increased in a time-dependent manner, although COX-1 mRNA was constantly expressed. Treatment with indomethacin, a potent inhibitor of PG biosynthesis, inhibited UV-induced ear swelling, abrogated local immunosuppression, and decreased the amount of PGE2 in the ear skin of XPA-deficient mice. These results indicate that the excess DNA photoproducts remaining in XPA-deficient cells after UV radiation may induce COX-2 expression. The induced production of PGE2 may be involved in the enhanced inflammation and immunosuppression caused by UV radiation in XPA-deficient mice and XP patients.
authors.affiliation: *Department of Dermatology, Kansai Medical University, Moriguchi, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kuwamoto
authors.forename: H
authors.initials: H
authors.lastname: Miyauchi-Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Eguchi
authors.forename: T
authors.initials: T
authors.lastname: Inui
authors.forename: Y
authors.initials: Y
authors.lastname: Urade
authors.forename: T
authors.initials: T
authors.lastname: Horio
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003600:Cytosol / Q000201:enzymology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004423:Ear / Q000528:radiation effects; D004487:Edema / Q000209:etiology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010741:Phospholipases A / Q000235:genetics; D010787:Photosensitivity Disorders / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010741:Phospholipases A; D015232:Dinoprostone; D015230:Prostaglandin D2; D007213:Indomethacin