title: Prostaglandin E₂ is critical for the development of niacin-deficiency-induced photosensitivity via ROS production.
abstract: Pellagra is a photosensitivity syndrome characterized by three "D's": diarrhea, dermatitis, and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis, the hallmark abnormality of this syndrome, remain unclear. We prepared niacin deficient mice in order to develop a murine model of pellagra. Niacin deficiency induced photosensitivity and severe diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently, photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. Moreover, enhanced PGE2 production in niacin deficiency was mediated via ROS production in keratinocytes. In line with the above murine findings, human skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was mediated through EP4 signaling in response to increased PGE2 production via induction of ROS formation.
authors.affiliation: 1] Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan [2] Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sugita
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ikenouchi-Sugita
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Haruna
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomura
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sakabe
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakahigashi
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Motonobu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D015120:6-Aminonicotinamide / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003872:Dermatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009525:Niacin / Q000037:antagonists & inhibitors / Q000172:deficiency*; D010787:Photosensitivity Disorders / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D017382:Reactive Oxygen Species; D009525:Niacin; D015120:6-Aminonicotinamide; D051546:Cyclooxygenase 2; D015232:Dinoprostone