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Effect of skin-derived antimicrobial peptide cathelicidin LL-37 on the regulation of skin barrier function

Research Project

Project/Area Number 26461703
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NIYONSABA Francois  順天堂大学, 医学(系)研究科(研究院), 先任准教授 (60365640)

Research Collaborator AKIYAMA Toshihiro  
KIATSURAYANON Chanisa  
UMEHARA Yoshie  
SMITHRITHEE Rithee  
IKEDA Shigaku  
OKUMURA Ko  
OGAWA Hideoki  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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ケラチノサイト / 抗菌物質 / タイトジャンクション / 皮膚免疫 / アトピー性皮膚炎 / 痒み / 炎症 / 抗菌ペプチド
Outline of Final Research Achievements

In this study, we evaluated the effects of LL-37 on regulation of keratinocyte tight junction (TJ) barrier function. We found that LL-37 increased the expression of TJ proteins and keratinocyte differentiation markers, and markedly strengthened the TJ barrier function via Rac1, atypical protein kinase C, glycogen synthase kinase-3 and PI3 kinase pathways. Similar to LL-37, humanβ-defensin-3 also enhanced the TJ barrier function. In addition, LL-37 induced the expression of semaphorin 3A, an itch inhibitor, implying LL-37 possible application to pruritus. Taken together, our findings that LL-37 andβ-defensin-3 enhance TJ barrier function, inhibit itch and inflammation suggest the potential use of skin-derived antimicrobial peptides for the understanding atopic dermatitis pathological mechanism and treatment.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (29 results)

All 2017 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 6 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 10 results) Funded Workshop (1 results)

  • [Journal Article] Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases.2017

    • Author(s)
      Niyonsaba F, Kiatsurayanon C, Chieosilapatham P, Ogawa H
    • Journal Title

      Experimental Dermatology

      Volume: - Issue: 11 Pages: 989-998

    • DOI

      10.1111/exd.13314

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] An antimicrobial peptide with angiogenic properties, AG-30/5C, activates human mast cells through the MAPK and NF-κB pathways.2016

    • Author(s)
      Kanazawa K, Okumura K, Ogawa H, Niyonsaba F.
    • Journal Title

      Immunol Res

      Volume: 64 Issue: 2 Pages: 594-603

    • DOI

      10.1007/s12026-015-8759-5

    • NAID

      130007632014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiogenic peptide (AG)-30/5C activates human keratinocytes to produce cytokines/chemokines and to migrate and proliferate via MrgX receptors.2016

    • Author(s)
      Kiatsurayanon C, Niyonsaba F, Chieosilapatham P, Okumura K, Ikeda S, Ogawa H.
    • Journal Title

      J Dermatol Sci

      Volume: 83 Issue: 3 Pages: 190-9

    • DOI

      10.1016/j.jdermsci.2016.05.006

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of human β-defensins in allergic diseases.2016

    • Author(s)
      Niyonsaba F, Kiatsurayanon C, Ogawa H
    • Journal Title

      Clinical and Experimental Allergy

      Volume: 46(12) Issue: 12 Pages: 1522-1530

    • DOI

      10.1111/cea.12843

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ヒトβ‐ディフェンシン類とアレルギー性疾患2016

    • Author(s)
      ニヨンサバ フランソワ
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 66(2) Pages: 146-151

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Novel insight into the role of antimicrobial (host defense) peptides/proteins in human skin diseases2016

    • Author(s)
      Niyonsaba F
    • Journal Title

      Juntendo Medical Journal

      Volume: 62(2) Pages: 120-131

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cathelicidin LL-37 induces semaphorin 3A production in human epidermal keratinocytes: implications for possible application to pruritus.2015

    • Author(s)
      Umehara Y, Kamata Y, Tominaga M, Niyonsaba F, Ogawa H, Takamori K.
    • Journal Title

      J Invest Dermatol

      Volume: 135 Issue: 11 Pages: 2887-2890

    • DOI

      10.1038/jid.2015.243

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Human β-defensin-3 increases the expression of interleukin-37 through CCR6 in human keratinocytes2015

    • Author(s)
      Smithrithee R, Niyonsaba F, Kiatsurayanon C, Ushio H, Ikeda S, Okumura K, Ogawa H
    • Journal Title

      Journal of Dermatological Science

      Volume: 77(1) Issue: 1 Pages: 46-53

    • DOI

      10.1016/j.jdermsci.2014.12.001

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The human cathelicidin LL-37 host defense peptide upregulates tight junction-related proteins and increases human epidermal keratinocyte barrier function.2014

    • Author(s)
      Akiyama T, Niyonsaba F, Kiatsurayanon C, Nguyen TT, Ushio H, Fujimura T, Ueno T, Okumura K, Ogawa H, Ikeda S
    • Journal Title

      J Innate Immun

      Volume: 6 Issue: 6 Pages: 739-53

    • DOI

      10.1159/000362789

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Host Defense (Antimicrobial) Peptide, Human β-Defensin-3, Improves the Function of the Epithelial Tight-Junction Barrier in Human Keratinocytes.2014

    • Author(s)
      Kiatsurayanon C, Niyonsaba F, Smithrithee R, Akiyama T, Ushio H, Hara M, Okumura K, Ikeda S, Ogawa H.
    • Journal Title

      J invest Deramatol

      Volume: 143 Issue: 8 Pages: 2163-73

    • DOI

      10.1038/jid.2014.143

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] The antimicrobial protein S100A7/psoriasin enhances expression of keratinocyte differentiation markers and strengthens the skin tight junction barrier2014

    • Author(s)
      Hattori F, Kiatsurayanon C, Okumura K, Ogawa H, Ikeda S, Okamoto K, Niyonsaba F
    • Journal Title

      British Journal of Dermatology

      Volume: 171(4) Issue: 4 Pages: 742-753

    • DOI

      10.1111/bjd.13125

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Effects of antimicrobial peptide LL-37 on expression of natural moisturizing factor-generating proteases in epidermal keratinocytes. The 41st Annual Meeting of the Japanese Society for Investigative Dermatology2016

    • Author(s)
      Umehara Y, Kamata Y, Tominaga M, Niyonsaba F, Sakaguchi A, Ogawa H, Takamori K
    • Organizer
      The 41st Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      仙台国際センター, 宮城, 仙台
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Antimicrobial peptide derived from IGFBP-5 (AMP-IBP5) stimulates various functions of human keratinocytes2016

    • Author(s)
      Chieosilapatham P, Niyonsaba F, Kiatsurayanon C, Okumura K, Ikeda S, Ogawa H
    • Organizer
      The 41st Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      仙台国際センター, 宮城, 仙台
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Immunomodulatory activities of novel synthetic host defense peptide, angiogenic peptide (AG)-30/5C, in human keratinocytes2016

    • Author(s)
      Niyonsaba F, Kiatsurayanon C, Chieosilapatham P, Okumura K, Ikeda S, Ogawa H
    • Organizer
      The 41st Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      仙台国際センター, 宮城, 仙台
    • Year and Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Immunomodulatory effects of the antimicrobial peptide derived from IGFBP-5 (AMP-IBP5) on normal human keratinocytes2016

    • Author(s)
      Chieosilapatham P, Niyonsaba F, Kiatsurayanon C, Okumura K, Ikeda S, Ogawa H
    • Organizer
      4th Eastern Asia Dermatology Congress
    • Place of Presentation
      Tokyo Bay Maihama Hotel Club Resort, 千葉, 浦安
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The roles of host defense protein S100A7/psoriasin in the skin2016

    • Author(s)
      Hattori F, Kiatsurayanon C, Ikeda S, Okumura K, Ogawa H, Okamoto K, Niyonsaba F
    • Organizer
      4th Eastern Asia Dermatology Congress
    • Place of Presentation
      Tokyo Bay Maihama Hotel Club Resort, 千葉, 浦安
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Skin-deried antimicrobial (host defense) peptides are multifunctional regulators of the skin immunity2016

    • Author(s)
      Niyonsaba F, Ikeda S, Ogawa H
    • Organizer
      4th Eastern Asia Dermatology Congress
    • Place of Presentation
      Tokyo Bay Maihama Hotel Club Resort, 千葉, 浦安
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] An angiogenic peptide AG-30/5C, stimulates various functions of human mast cells2016

    • Author(s)
      Kanazawa K, Okumura K, Ogawa H, Niyonsaba F
    • Organizer
      16th International Congress of Immunology
    • Place of Presentation
      Melbourne Convention and Exhibition Centre, Victoria, Melbourne
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Antimicrobial peptide derived from IGFBP-5 (AMP-IBP5) stimulates normal human keratinocytes beyond direct antimicrobial properties2016

    • Author(s)
      Chieosilapatham P, Niyonsaba F, Kiatsurayanon C, Okumura K, Ikeda S, Ogawa H
    • Organizer
      16th International Congress of Immunology
    • Place of Presentation
      Melbourne Convention and Exhibition Centre, Victoria, Melbourne
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Antimicrobial peptide derived from insulin-like growth factor-binding protein 5, AMP-IBP5, activates human mast cells2016

    • Author(s)
      Niyonsaba F, Okumura K, Ogawa H
    • Organizer
      16th International Congress of Immunology
    • Place of Presentation
      Melbourne Convention and Exhibition Centre, Victoria, Melbourne
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of antimicrobial peptides on expression of exon guidance molecules in normal human epidermal keratinocytes2015

    • Author(s)
      Umehara Y, Kamata Y, Tominaga M, Niyonsaba F, Ogawa H, Takamori K
    • Organizer
      日本研究皮膚科学会 第40年次学術大会・総会
    • Place of Presentation
      岡山県、岡山市
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Host defense protein S100A7/psoriasin regulates pores in the epidermis: aquaporins and tight junctions2015

    • Author(s)
      Hattori F, Ikeda S, Okumura K, Tominaga M, Takamori K, Ogawa H, Okamoto K, Niyonsaba F
    • Organizer
      日本研究皮膚科学会 第40年次学術大会・総会
    • Place of Presentation
      岡山県、岡山市
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
  • [Presentation] The novel antimicrobial peptide derived from insulin-like growth factor-binding protein 5 (AMP-IBP5) activates normal human keratinocytes2015

    • Author(s)
      Chieosilapatham P, Niyonsaba F, Kiatsurayanon C, Okumura K, Ikeda S, Ogawa H
    • Organizer
      日本研究皮膚科学会 第40年次学術大会・総会
    • Place of Presentation
      岡山県、岡山市
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Angiogenic peptide (AG)-30/5C activates human keratinocytes to produce cytokines/chemokines, migrate and proliferate via MrgX receptors2015

    • Author(s)
      Kiatsurayanon C, Niyonsaba F, Ikeda S, Okumura K, Ogawa H
    • Organizer
      日本研究皮膚科学会 第40年次学術大会・総会
    • Place of Presentation
      岡山県、岡山市
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Angiogenic peptide-30 (AG-30) activates primary human keratinocytes to produce cytokines/ chemokines via MrgX receptors2015

    • Author(s)
      Kiatsurayanon C, Niyonsaba F, Ushio H, Ikeda S, Okumura K, Ogawa H
    • Organizer
      2015 Annual Meeting of the Society for Investigative Dermatology
    • Place of Presentation
      Atlanta, Georgia
    • Year and Date
      2015-05-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tight junction barrier enhancement of human beta-defensin-3 in human keratinocytes2014

    • Author(s)
      Kiatsurayanon C, Niyonsaba F, Akiyama T, Ushio H, Okumura K, Ikeda S, Ogawa H
    • Organizer
      3rd Eastern Asia Dermatology Congress
    • Place of Presentation
      済州島、韓国
    • Year and Date
      2014-09-24 – 2014-09-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Possible roles of host defense protein S100A7/Psoriasin in regulation of skin barrier functions2014

    • Author(s)
      Hattori F, Kiatsurayanon C, Okumura K, Ogawa H, Ikeda S, Okamoto K, Niyonsaba F
    • Organizer
      3rd Eastern Asia Dermatology Congress
    • Place of Presentation
      済州島、韓国
    • Year and Date
      2014-09-24 – 2014-09-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Effects of human beta-defensins on the epithelial tight junction barrier2014

    • Author(s)
      Kiatsurayanon C, Niyonsaba F, Akiyama T, Ushio H, Ikeda S, Okumura K, Ogawa H
    • Organizer
      第113回日本皮膚科学会総会
    • Place of Presentation
      国立京都国際会館 、京都、日本
    • Year and Date
      2014-05-30 – 2014-06-01
    • Related Report
      2014 Research-status Report
  • [Funded Workshop] 16th International Congress of Immunology2016

    • Place of Presentation
      Melbourne Convention and Exhibition Centre, Victoria, Melbourne
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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