Cutaneous immune responses to niacin in photosensitivity

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791302
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: SUGITA Kazunari 産業医科大学, 医学部, 助教 (40412647)
• Project Period (FY): 2011 – 2012
• Keywords: 皮膚炎症 / 再生学

Research 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 underlying the hallmark abnormalities of this syndrome are unclear. Here we show that enhanced photosensitivity in mice was induced by treatment with a niacin antagonist as well as niacin-deficient diets, and that severe diarrhea with weight loss was induced by treatment with the niacin ntagonist, which suggest that this is a model of pellagra. Intriguingly, the niacin antagonist induced elevated expression of COX-2 and PGE syntheses (Ptges) mRNAs. The niacin antagonist treatment-induced photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. In line with the above findings in mice, analysis of skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Taken together, these findings indicate that niacin deficiency results in the development of photosensitivity in pellagra mediated by signaling through EP4 in response to increased PGE production.

Research Products

• [Journal Article] Role of prostaglandin E2 for photosensitivity of murine pellagra model (2011)
  • Author(s): Sugita K, Kabashima K, Sakabe J, Kuroda,Nakamura M, and Tokura Y
  • Journal Title: Photomedicine and Photobiology Volume: 33 Pages: 3-4
• [Presentation] Role of prostaglandin E2-EP2/EP4 signaling in the development of photosensitivity in pellagra (2012)
  • Author(s): Sugita K, Kabashima K, Jun-ichi Sakabe, Nakahigashi K, Kuroda E, Uematsu S, Akira S, Nakamura M, Naruymiya S, Miyachi Y, and Tokura Y
  • Organizer: 37th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa, Japan
  • Year and Date: 2012-12-08
• [Presentation] Role of prostaglandin E2-EP2/EP4 signaling in the development of photosensitivity in pellagra (2012)
  • Author(s): Sugita K, Nomura T, Jun-ichi Sakabe, Nakahigashi K, Kuroda E, Uematsu S, Akira S, Nakamura M, Miyachi Y, Tokura Y,and Kabashima K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-06
• [Presentation] Role of prostaglandin E2-EP2/EP4 signaling in the development of photosensitivity in pellagra (2012)
  • Author(s): Sugita K, Kabashima K, Jun-ichi Sakabe, Nakahigashi K, Kuroda E, Uematsu S, Akira S, Nakamura M, Narumiya S, Miyachi Y, and Tokura Y
  • Organizer: IEIIS2012
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-10-25
• [Presentation] Establishment and PGE2 requirement of a new mouse model for pellagra (2011)
  • Author(s): Sugita K, Kabashima K, Sakabe J, Kuroda E, Nakamura M, and Tokura Y
  • Organizer: 41st Annual European Society for Dermatological Research Meeting
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2011-09-08
• [Presentation] 光線過敏症におけるナイアシンの役割 (2011)
  • Author(s): 杉田和成, 椛島健治, 坂部純一,黒田悦史, 中村元信, 戸倉新樹
  • Organizer: 第33回日本光医学.光生物学会
  • Place of Presentation: 大阪
  • Year and Date: 2011-07-22