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The role of IL-33 in the dysfunction of skin barrier

Research Project

Project/Area Number 16K10172
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionJichi Medical University

Principal Investigator

Komine Mayumi  自治医科大学, 医学部, 教授 (00282632)

Research Collaborator Jin Meijuan  
Tsuda Hidetoshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsIL-33 / 有棘層 / トランスジェニックマウス / 表皮細胞 / 炎症 / 皮膚炎 / IL-33 / 皮膚バリア機能
Outline of Final Research Achievements

Transgenic mice expressing IL-33 in the suprabasal layer of epidermal keratinocytes were generated, by utilizing involucrin promoter. Transgenic mice grew slower and small, and died in 4th week. Skin, lung, lymph node and spleen was harvested in 3rd week, and histologically, immunohistochemically studied. RNA was extracted from each sample, which was subjected to DNA microarray. IL-33Tg mice showed very strong inflammation in hands and feet, with extensive inflammatory cells in the joints. The results of microarray is now being analyzed.

Academic Significance and Societal Importance of the Research Achievements

IL-33はTh2タイプのサイトカインとして広く認識されているが、それ以外の働きについては不明な点が多い。IL-33は炎症性皮膚疾患では有棘層に強く発現するため、有棘層に発現するIL-33の役割を解明することにより、皮膚疾患の病態解明につながる。今回の結果は、有棘層に発現するIL-33が、外力の影響を受けやすい手足に非常に強い炎症を惹起することを示しており、乾癬などの炎症性皮膚疾患における有棘層ケラチノサイトのIL-33発現が、乾癬の病態に関与している可能性が示唆された。この結果は、炎症性皮膚疾患の治療開発において新たなステップとなる可能性がある。

Report

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

    (26 results)

All 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 11 results) Book (1 results)

  • [Journal Article] Interleukin-33 is expressed in the lesional epidermis in herpes virus infection but not in verruca vulgaris.2018

    • Author(s)
      Jin M., Komine M., Tsuda H., Oshio T., Ohtsuki M.
    • Journal Title

      J Dermatol

      Volume: 45 Issue: 7 Pages: 855-857

    • DOI

      10.1111/1346-8138.14334

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methotrexate, but not narrowband ultraviolet B radiation, suppresses interleukin-33 mRNA levels in psoriatic plaques and protein levels in serum of patients with psoriasis2018

    • Author(s)
      Meephansan Jitlada、Subpayasarn Urairack、Ponnikorn Saranyoo、Chakkavittumrong Panlop、Juntongjin Premjit、Komine Mayumi、Ohtsuki Mamitaro、Poovorawan Yong
    • Journal Title

      The Journal of Dermatology

      Volume: 45 Issue: 3 Pages: 322-325

    • DOI

      10.1111/1346-8138.14009

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Differential expression of alarmins: IL-33 as a candidate marker for early diagnosis of toxic epidermal necrolysis.2018

    • Author(s)
      Adachi A., Komine M., Tsuda H., Nakajima S., Kabashima K., Ohtsuki M.
    • Journal Title

      J Allergy Clin Immunol Pract.

      Volume: 7 Issue: 1 Pages: 325-327

    • DOI

      10.1016/j.jaip.2018.05.037

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Real-world use of apremilast for patients with psoriasis in Japan2018

    • Author(s)
      Kishimoto Megumi、Komine Mayumi、Hioki Tomoyuki、Kamiya Koji、Sugai Junichi、Ohtsuki Mamitaro
    • Journal Title

      The Journal of Dermatology

      Volume: 45 Issue: 11 Pages: 1345-1348

    • DOI

      10.1111/1346-8138.14617

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of M2 macrophages in the pathomechanisms of multicentric reticulohistiocytosis.2017

    • Author(s)
      Kamiya K, Komine M, Murata S, Ohtsuki M.
    • Journal Title

      Journal of Dermatology

      Volume: 56 Issue: 8

    • DOI

      10.1111/ijd.13661

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial.2017

    • Author(s)
      Ohtsuki M, Okubo Y, Komine M, Imafuku S, Day RM, Chen P, Petric R, Maroli A, Nemoto O.
    • Journal Title

      Journal of Dermatology

      Volume: 44 Issue: 8 Pages: 873884-873884

    • DOI

      10.1111/1346-8138.13829

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diagnosis of pseudoxanthoma elasticum in a 4-year-old boy2017

    • Author(s)
      Maki N., Komine M., Tsuda H., Fujita Y., Fujita E., Murata S., Demitsu T., Utani A., Ohtsuki M.
    • Journal Title

      J Dertmatol

      Volume: 印刷中 Issue: 2 Pages: 244-236

    • DOI

      10.1111/1346-8138.13805

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of promoter region of human IL-33 responsive to induction by IFNγ2017

    • Author(s)
      Tsuda H., Komine M., Tominaga S., Ohtsuki M.
    • Journal Title

      J Dermatol Sci

      Volume: 85 Issue: 2 Pages: 137-140

    • DOI

      10.1016/j.jdermsci.2016.11.002

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Nuclear ezpression of IL-33 in epidermal keratinocytes promotes wound healing in mice2017

    • Author(s)
      Oshio T., Komine M., Tsuda H., Tominaga S., Saito H., Nakae S., Ohtsuki M.
    • Journal Title

      J Dermatol Sci

      Volume: 85 Issue: 2 Pages: 106-114

    • DOI

      10.1016/j.jdermsci.2016.10.008

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adalimumab administration after infliximab therapy is a successful treatment strategy for generalized pustular psoriasis.2017

    • Author(s)
      Matsumoto A, Komine M, Karakawa M, Kishimoto M, Ohtsuki M.
    • Journal Title

      Journal of Dermatology

      Volume: - Issue: 2 Pages: 202-204

    • DOI

      10.1111/1346-8138.13632

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of maxacalcitol ointment on skin lesions in patients with psoriasis receiving treatment with adalimumab.2016

    • Author(s)
      Karakawa M, Komine M, Kishimoto M, Maki N, Matsumoto A, Sugai J, Ohtsuki M
    • Journal Title

      Journal of Dermatology

      Volume: 43 Issue: 11 Pages: 1354-1357

    • DOI

      10.1111/1346-8138.13515

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Poly I:CはTLR3-IRF3を介して IL-33をプロモーターレベルで誘導する2018

    • Author(s)
      小宮根真弓、金 美娟、津田英利、大槻マミ太郎
    • Organizer
      日本炎症・再生医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 表皮細胞に対するアプレミラストの作用についての検討2018

    • Author(s)
      金 美娟、小宮根真弓、津田英利、大槻マミ太郎
    • Organizer
      山梨地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] IL-33 determines the type of inflammation in psoriasis mice model2018

    • Author(s)
      Hidetoshi Tsuda, Mayumi Komine, Tomoyuki Hioki, Susumu Nakae, Mamitaro Ohtsuki
    • Organizer
      Inflammatory Skin Disease Summit
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 表皮角化細胞へのTNFα刺激はIL-33の発現を抑制する2018

    • Author(s)
      津田英利、小宮根真弓、大槻マミ太郎
    • Organizer
      分子皮膚科フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] The double-stranded RNA induces IL-33 promoter activation through TLR3-IRF3 pathway, depending on EGF receptor activation in normal human epidermal keratinocytes2017

    • Author(s)
      Jin M, Komine M, Tsuda H, Tominaga S, Ohtsuki M.
    • Organizer
      76th Annual Meeting of Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Toll-like receptor 3 activation results in IL-33 promoter activation through IRF3 transcription factor depending on EGF receptor activation in normal human epidermal keratinocytes.2017

    • Author(s)
      Jin M, Komine M, Tsuda H, Ohtsuki M.
    • Organizer
      42nd Annual Meeting of Japanese Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nuclear IL-33 knock down by siRNA impairs cell division and cell motility of normal human epidermal keratinocytes2017

    • Author(s)
      Tsuda H, Komine M, Ohtsuki M.
    • Organizer
      76th Annual Meeting of Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Loss of IL-33 alters cytokine profile in imiquimod-induced psoriasis model2017

    • Author(s)
      Tsuda H, Komine M, Ohtsuki M.
    • Organizer
      42nd Annual Meeting of Japanese Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] STAT3 activation causes IL-33 expression in normal human epidermal keratinocyte2017

    • Author(s)
      Tsuda H, Komine M, Ohtsuki M.
    • Organizer
      47th Annual Meeting of European Society for Dermatological Research
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of Oncostatin M signaling in Hemangiosarcoma Cell Line and Regulation of IL-33 Expression2016

    • Author(s)
      Hidetoshi Tsuda, Mayumi Komine, Meijuan Jin, Naomi Nakano, Shin-ichi Tominaga, Mikio Masuzawa, Mamitaro Ohtsuki
    • Organizer
      41th Annual Meeting of Japanese Society for Investigative Dermatology
    • Place of Presentation
      仙台国際センター、宮城県、仙台市
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Double-stranded RNA induces IL-33 expression through activation of EGFR, ERK, p38 and TBK-1 in normal epidermal keratinocytes.2016

    • Author(s)
      Meijuan Jin, Mayumi Komine, Hidetoshi Tsuda, Shin-ichi Tominaga, Mamitaro Ohtsuki
    • Organizer
      41th Annual Meeting of Japanese Society for Investigative Dermatology
    • Place of Presentation
      仙台国際センター、宮城県、仙台市
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The loss of nuclear IL-33 affects cell division of normal human keratinocyte2016

    • Author(s)
      Hidetoshi Tsuda, Mayumi Komine, Shin-ichi Tominaga, Mamitaro Ohtsuki
    • Organizer
      46th Annual Meeting of European Society for Dermatological Research
    • Place of Presentation
      Munchen, Germany
    • Year and Date
      2016-09-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Double-stranded RNA induces IL-33 expression through activation of EGFR, ERK, and p38 in normal human epidermal keratinocytes.2016

    • Author(s)
      Meijuan Jin, Mayumi Komine, Hidetoshi Tsuda, Mamitaro Ohtsuki
    • Organizer
      46th Annual Meeting of European Society for Dermatological Research
    • Place of Presentation
      Munchen, Germany
    • Year and Date
      2016-09-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] IL-33 is expressed in lesional skin of herpes virus infection,but not of verruca vulgaris.2016

    • Author(s)
      Meijuan Jin, Mayumi Komine, Hidetoshi Tsuda, Shin-ichi Tominaga, Mamitaro Ohtsuki
    • Organizer
      75th Annual Meeting of Society for Investigative Dermatology
    • Place of Presentation
      Scottsdale, USA
    • Year and Date
      2016-05-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] Psoriasis2017

    • Author(s)
      Jitlada Meephansan, Urairack Subpayasarn, Mayumi Komine, and Mamitaro Ohtsuki
    • Publisher
      Intech
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-01-27  

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