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The development a new treatment for Palmoplantar pustulosis with improving the abnormal antimicrobial peptide expression

Research Project

Project/Area Number 16K10128
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionEhime University

Principal Investigator

murakami masamoto  愛媛大学, 医学系研究科, 准教授 (20278302)

Research Collaborator Tsuda Teruko  
Tan Eriko  
Kameda Kenji  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords掌蹠膿疱症 / 抗菌ペプチド / hCAP-18 / TLN-58 / エクリン汗腺 / cathelicidin / 皮膚病態学
Outline of Final Research Achievements

The abnormal fragment of hCAP-18 in PPP vesicle was searched with several experiments, and TLN-58 was confirmed. The responsible proteinase was searched with MASCOT database, and neutrophilic elastase was found in the database. As a proteinase inhibitor for it, alpha one antitrypsin was selected and tested if it could suppress the protein processing of hCAP-18 to TLN-58, and we could confirm the prevention of processing. TLN-58 synthetic peptide induces the inflammatory response in primary keratinocyte culture and LSE, but not in sweat gland cells (NCL-SG3), especially for IL-8, comparing with LL-37. In the mouse model, the peptide could induce inflammatory changes in skin tissue, too. However, the proteinase inhibitor induced inflammatory response as an irritant, so that we failed to establish it as a new treatment for PPP.

Academic Significance and Societal Importance of the Research Achievements

掌蹠膿疱症の病態に関わる因子がまた新たに一つ同定された。水疱内容における異常な抗菌ペプチドの発現様式が本疾患の病態に関わることが明らかとなり、将来の治療オプションを考える上で、重要な発見となった。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results) Presentation (3 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Diagnostic histopathological features distinguishing palmoplantar pustulosis from pompholyx2019

    • Author(s)
      Masuda‐Kuroki Kana、Murakami Masamoto、Kishibe Mari、Kobayashi Satomi、Okubo Yukari、Yamamoto Toshiyuki、Terui Tadashi、Sayama Koji
    • Journal Title

      The Journal of Dermatology

      Volume: 46 Issue: 5 Pages: 399-408

    • DOI

      10.1111/1346-8138.14850

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced-HMGB1 suppresses poly(I:C)-induced inflammation in keratinocytes2018

    • Author(s)
      Hideki Mori, Masamoto Murakami, Teruko Tsuda, Kenji Kameda, Ryo Utsunomiya, Kana Masuda, Ken Shiraishi, Xiuju Dai, Mikiko Tohyama, Hiroki Nakaoka, Koji Sayama
    • Journal Title

      Journal of DermatologicalScience

      Volume: 90 Issue: 2 Pages: 154-165

    • DOI

      10.1016/j.jdermsci.2018.01.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Efficacy and Safety of Guselkumab, an Anti?interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis2018

    • Author(s)
      Terui Tadashi、Kobayashi Satomi、Okubo Yukari、Murakami Masamoto、Hirose Keiichiro、Kubo Hiroshi
    • Journal Title

      JAMA Dermatology

      Volume: 154 Issue: 3 Pages: 309-309

    • DOI

      10.1001/jamadermatol.2017.5937

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparinoid suppresses Der p-induced IL-1β production by inhibiting ERK and p38 MAPK pathways in keratinocytes2018

    • Author(s)
      Utsunomiya Ryo、Dai Xiuju、Murakami Masamoto、Masuda Kana、Okazaki Hidenori、Tsuda Teruko、Mori Hideki、Shiraishi Ken、Tohyama Mikiko、Sayama Koji
    • Journal Title

      Experimental Dermatology

      Volume: 27 Issue: 9 Pages: 981-988

    • DOI

      10.1111/exd.13685

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The microbiome of the “sterile” pustules in palmoplantar pustulosis2018

    • Author(s)
      Masuda-Kuroki Kana、Murakami Masamoto、Tokunaga Naohito、Kishibe Mari、Mori Hideki、Utsunomiya Ryo、Tsuda Teruko、Shiraishi Ken、Tohyama Mikiko、Sayama Koji
    • Journal Title

      Experimental Dermatology

      Volume: 27 Issue: 12 Pages: 1372-1377

    • DOI

      10.1111/exd.13791

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TLN-58, an Additional hCAP18 Processing Form, Found in the Lesion Vesicle of Palmoplantar Pustulosis in the Skin.2017

    • Author(s)
      Murakami M, Kameda K, Tsumoto H, et al.
    • Journal Title

      J Invest Dermatol.

      Volume: 137 Issue: 2 Pages: 322-331

    • DOI

      10.1016/j.jid.2016.07.044

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] New role of exogenous HMGB1 for human keratinocyte under acute inflammatory event.2018

    • Author(s)
      Mori H, Murakami M, Utsunomiya R, Masuda K, Shiraishi K, Dai X, Tohyama M, Sayama.
    • Organizer
      International Investigative Dermatology Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The microbiome exists in the ‘sterile’ pustule of palmoplantar pustulosis.2018

    • Author(s)
      Masuda K, Murakami M, Tokunaga N, Kishibe M, Mori H, Utsunomiya R, Tsuda T, Shiraishi K, Tohyama M, Sayama K.
    • Organizer
      International Investigative Dermatology Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The character of TLN-58, newly discovered hCAP18 processing form, found in the lesion vesicle of palmoplantar pustulosis in the skin2016

    • Author(s)
      Masamoto Murakami, Kenji Kameda, Hideki Mori, et al.
    • Organizer
      44th Annual ESDR Meeting
    • Place of Presentation
      Munchen
    • Year and Date
      2016-09-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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