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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10135
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Jichi 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
• Keywords: ケラチノサイト / IL-33 / 細胞分裂 / 細部増殖 / 乾癬 / siRNA

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.

Free Research Field

皮膚科学

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。