New barrier function of stratum corneum and its regulation in inflammatory skin diseases

• Project/Area Number: 26461688
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Gifu University
• Principal Investigator: Kanoh Hiroyuki 岐阜大学, 大学院医学系研究科, 准教授 (40566494)
• Co-Investigator(Kenkyū-buntansha): 清島 眞理子 岐阜大学, 大学院医学系研究科, 教授 (00171314) ; 稲垣 直樹 岐阜薬科大学, 薬学部, 教授 (30137062) ; 中村 光浩 岐阜薬科大学, 薬学部, 教授 (30433204) ; 大澤 陽介 東京都立駒込病院(臨床研究室), 肝臓内科, 医長 (60447787)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 角層バリア機構 / セラミド / サイトカイン / インターフェロン-γ / IFN-γ / 角層脂質 / 長鎖脂肪酸セラミド / バリア機能 / アトピー性皮膚炎 / インターフェロンγ / 乾癬 / interferon gamma

Outline of Final Research Achievements

Ceramide plays an important role in the stratum corneum barrier functions as a major component of the intercellular lipid of corneocytes. It has recently been shown that the average fatty acid (FA) chain length of ceramide correlates with the barrier function and is decreased in atopic dermatitis. We have previously shown that the expression of elongase of very long-chain fatty acid (ELOVL) and ceramide synthase (CerS), the key enzymes in the long-chain FA ceramide synthesis, is decreased by IFN-γ in cultured keratinocytes. In the present study, analysis of dermatitis caused by repeated exposure of mouse ear to mite antigen or imiquimod showed that increased expression of IFN-γ was correlated with decreased expression of ELOVL and CerS and decrease in long-chain FA ceramide. These results strongly suggest that, in dermatitis where local expression of IFN-γ is increased, IFN-γ may disrupt skin barrier function by inducing compositional change in stratum corneum ceramide.

Research Products

• [Presentation] IFN-γ may disrupt skin barrier function through reduction of long-chain fatty acid ceramides in mite-induced dermatitis (2017)
  • Author(s): Hiroyuki Kanoh, Asako Ishitsuka, Mitsuhiro Nakamura, Naoki Inagaki, Hiroyasu Ito, Yoshiko Banno, Mariko Seishima
  • Organizer: 76th Annual meeting of the Society for Investigative Dermatology
  • Place of Presentation: Portland, Oregon, USA
  • Year and Date: 2017-04-26
  • Int'l Joint Research
• [Presentation] Reduction of long-chain fatty acid ceramides in dermatitis caused by repeated exposure to house-dust mite in NC/Nga mice (2016)
  • Author(s): Hiroyuki Kanoh, Asako Ishitsuka, Etsuko Fujine, Shuhei Matsuhaba, Mitsuhiro Nakamura, Naoki Inagaki, Yoshiko Banno, Mariko Seishima
  • Organizer: The 41st Annual meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 仙台
  • Year and Date: 2016-12-09
• [Presentation] Decreased expression of ELOVL and ceramide synthase in dermatitis caused by repeated exposure to house-dust mite in NC/Nga mice (2015)
  • Author(s): Kanoh H, Ishitsuka A, Fujine E, Matsuhaba S, Nakamura M, Inagaki N, Banno Y, Mariko Seishima M
  • Organizer: The 40th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 岡山
  • Year and Date: 2015-12-11
• [Presentation] Effects of interferon-gamma on expression of ceramide synthases and elongases of long-chain fatty acids in cultured human keratinocytes (2014)
  • Author(s): Yasue Y, Ishitsuka A, Fujine E, Banno Y, Kanoh H, Seishima M
  • Organizer: The 39th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-12 – 2014-12-14