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Analysis of IL-33 function for cell division and proliferation in normal human epidermal keratinocytes

Research Project

Project/Area Number 16K10135
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

Tduda Hidetoshi  自治医科大学, 医学部, ポスト・ドクター (30414923)

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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsケラチノサイト / IL-33 / 細胞分裂 / 細部増殖 / 乾癬 / siRNA / 細胞局在 / Th17 / 細胞増殖 / 乾癬モデルマウス / 細胞質分裂 / 細胞収縮管 / 細胞遊走能 / 皮膚科学
Outline of Final Research Achievements

IL-33 is expressed in nucleus of epithelial and endothelial cells, and knockdown of IL-33 increased binucleated cells and decreased cell proliferation in normal human epidermal keratinocytes (NHEKs). This cause was to attenuate function of contractile ring for cytokinesis. Time laps observation revealed that cell division failed to cytokinesis. In the other hand, IL-33 expression plasmids which expressed various length of IL-33 were transfected to NHEKs, and it was irradiated UVB. IL-33 transfected NHEKs did not gain the tolerance for UVB. And addition, IL-33 transfected cells did not obtain cell proliferation. In order to examine the function of IL-33 against to psoriasis, it was investigated imiquimod induced mouse model. Imiquimod induced inflammation was significantly reduced in IL-33KO mice.

Academic Significance and Societal Importance of the Research Achievements

これまで、喘息の悪性因子としてTh2やILC2を活性化するサイトカインとしての報告が多く、皮膚科学領域においてもアトピー性皮膚炎や乾癬の重症度血中濃度が相関するという報告が見られる。これまでも核内転写因子として働くとする報告はいくつか見られたが、細胞機能の変化まで見た報告はこれまでには無い。今回新たにIL-33の機能を見つけたことは、学術的には非常に意義があることであり、疾患治療のターゲットとしてマルチな効果を発揮するものと考えられる。

Report

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

    (18 results)

All 2018 2017 2016

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 5 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] 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] Generalized pustular psoriasis in a 92-year-old man with a homozygous nonsense mutation in IL36RN2018

    • Author(s)
      Ueda Y, Komine M, Kamiya K, Tsuda H, Maekawa T, Murata S, Ohtsuki M
    • Journal Title

      J Dermatol

      Volume: 45(3) Issue: 3 Pages: 326-328

    • DOI

      10.1111/1346-8138.14132

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [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
      2018 Annual Research Report 2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [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
      2016 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
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Case of generalized pustular psoriasis exacerbated during pregnancy, successfully treated with infliximab2016

    • Author(s)
      Adachi A., Komine M., Hirano T., Tsuda H., Karakawa M., Murata S., Ohtsuki M.
    • Journal Title

      J Dertmatol

      Volume: 43 Issue: 12 Pages: 1439-1440

    • DOI

      10.1111/1346-8138.13429

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] TNFα suppressed IL-33 expression induced by STAT1 and STAT3 dependent signal2018

    • Author(s)
      Hidetoshi Tsuda, Mayumi Komine, Mamitaro Ohtsuki
    • Organizer
      International Investigative Dermatology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TNFαは正常ヒト表皮角化細胞においてFli1の発現を誘導することによって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
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Double-stranded RNA induces IL-33 promoter activation through TLR3-IRF3 pathway, depending on EGF receptor activation in normal human epidermal keratinocytes.2017

    • Author(s)
      Jin, M., Komine, M., Tsuda, H., Tominaga, S., Ohtsuki, M
    • Organizer
      76th Annual Meeting Society for Investigative Dermatology (SID)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nuclear IL-33 promotes wound healing by sustaining cell division and motility through regulating actin filament re-construction2017

    • Author(s)
      Tsuda, H., Oshio, T., Komine, M., Tominaga, S., Ohtsuki, M.
    • Organizer
      76th Annual Meeting Society for Investigative Dermatology (SID)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Expression of factors regulating cytokinesis in Bowen’s disease2017

    • Author(s)
      Okada, H., Komine, M., Tsuda, H., Kamiya, K., Jin, M., Ohtsuki, M.
    • Organizer
      The 47th Annual Meeting European Society for Dermatological Research (ESDR)
    • 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
      The 47th Annual Meeting European Society for Dermatological Research (ESDR)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 一時的な核内のIL-33の消失は表皮角化細胞の細胞分裂を抑制する2017

    • Author(s)
      津田英利, 小宮根真弓, 大槻マミ太郎
    • Organizer
      生命科学系学会合同年次大会 ConBio2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Loss of IL-33 alters cytokine profile in imiquimod-induced psoriasis model2017

    • Author(s)
      Tsuda, H., Komine, M., Nakae, S., Ohtsuki, M.
    • Organizer
      The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology (JSID)
    • Related Report
      2017 Research-status Report
  • [Presentation] Analysis of Oncostatin M signaling in hemangiosarcoma cell line and regulation of IL-33 expression2016

    • Author(s)
      Tsuda H., Komine M., Jin M., Nakano N., Tominaga S., Masuzawa M., Ohtsuki M.
    • Organizer
      第41回日本研究皮膚科学会学術大会
    • Place of Presentation
      仙台国際センター、仙台、宮城県、日本
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
  • [Presentation] IL-33 is essential in cell division of normal human epidermal keratinocytes in transient knock-down experiment2016

    • Author(s)
      Tsuda H., Komine M., Jin M., Tominaga S., Ohtsuki M.
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜、横浜、神奈川県、日本
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] The loss of nuclear IL-33 affects cell division of normal human keratinocyte2016

    • Author(s)
      Tsuda H., Komine M., Tomninaga S., Ohtsuki M.
    • Organizer
      第46回欧州研究皮膚科学会学術大会
    • Place of Presentation
      Technical University of Munich, ミュンヘン, ドイツ
    • Year and Date
      2016-09-05
    • Related Report
      2016 Research-status Report

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

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