Analyses of eccrine sweat reveal pathogenesis of atopic dermatitis

• Project/Area Number: 24659532
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Ehime University
• Principal Investigator: SAYAMA Koi 愛媛大学, 医学(系)研究科(研究院), 教授 (80187286)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アトピー性皮膚炎 / 汗 / 角化細胞 / バリア異常 / IL-1 / IL-31 / エクリン汗 / バリア障害 / 自然免疫

Research Abstract

Eccrine sweat was collected from the arms of healthy volunteers after exercise, and levels of proinflammatory cytokines in the sweat were quantified by ELISA. We detected the presence of IL-1alpha, IL-1beta, and high levels of IL-31 in sweat samples. To investigate whether sweat activates keratinocytes, normal human keratinocytes were stimulated with concentrated sweat. Western blot analysis demonstrated the activation of NF-kB, ERK, and JNK signaling in sweat-stimulated keratinocytes. Real-time PCR using total RNA and ELISA analysis of supernatants showed the upregulation of IL-8 and IL-1beta by sweat. Furthermore, pretreatment with IL-1R antagonist blocked sweat-stimulated cytokine production and signal activation, indicating that bioactive IL-1 is a major factor in the activation of keratinocytes by sweat.

Research Products

• [Journal Article] Eccrine sweat contains IL-1α, IL-1βand IL-31 and activates epidermal keratinocytes as a danger signal (2013)
  • Author(s): Dai X, Okazaki H, Hana awa Y, Murakami M, Tohyama M, Shirakata Y, Sayama K
  • Journal Title: PLoS One Volume: 8(7)
• [Journal Article] Eccrine sweat contains IL-1α, IL-1β and IL-31 and activates epidermal keratinocytes as a danger signal. (2013)
  • Author(s): Dai X, Okazaki H, Hanakawa Y, Murakami M, Tohyama M, Shirakata Y, Sayama K.
  • Journal Title: PLoS One. Volume: ８ Issue: 7 Pages: 1-8
  • DOI: 10.1371/journal.pone.0067666
  • Peer Reviewed
• [Journal Article] INF-alpha Enhances IL-22 Receptor Expression in Keratinocytes:A Possible Role in the Development of Psoriasis. (2012)
  • Author(s): Tohyama M, Yang L, Hanakawa Y, Dai X, Shirakata Y, and Sayama K.
  • Journal Title: J Invest Dermatol; Volume: 132 Issue: 5 Pages: 1933-1935
  • DOI: 10.1007/s00109-009-0457-0
  • Peer Reviewed
• [Presentation] Eccrine sweat stimulates the release of IL-8 via IL-1 from epidermal keratinocytes as danger signal (2013)
  • Author(s): Okazaki H, Dai H, Murakami M, Hanakawa Y, Tohyama M, Shirakata Y, Sayama K
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh, UK
• [Presentation] Eccrine sweat simulates the release of IL-8 via IL-1 from epidermal keratinocytes as danger signal (2013)
  • Author(s): Okazaki H, Dai X, Murakami M, Hanakawa Y, Tohyama M, Shirakata Y, and Sayama K.
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh, UK
• [Presentation] Autophagy is induced by differentiation in epidermal keratinocytes. (2012)
  • Author(s): 1. Dai X, Okazaki H, Hanakawa Y, Shirakata Y, Murakami M, Tohyama M, and Sayama K.
  • Organizer: 42nd Annual ESDR Meeting
  • Place of Presentation: Venice, Italy