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Role of AIF-1 in pathogenesis of pulmonary fibrosis and development of its treatment

Research Project

Project/Area Number 16K09900
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

KAWAHITO YUTAKA  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50336731)

Co-Investigator(Kenkyū-buntansha) 河野 正孝  京都府立医科大学, 医学(系)研究科(研究院), 講師 (60405256)
Research Collaborator NAGAHARA HIDETAKE  
KIDA TAKASHI  
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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsAIF-1 / 肺線維症 / ブレオマイシン / 膠原病学
Outline of Final Research Achievements

AIF-1 is expressed in BALF in acute phase of bleomycin induced lung injury mouse model. TNF-α and IL-6 secreted from AIF stimulated macrophages and lung fibroblasts caused inflammation and tissue destruction. KC (CXCL1) is secreted form AIF stimulated lung fibroblasts inducing chemotaxis. In the chronic phase, AIF-1 is expressed in macrophages, secreting TGF-β, which is a growth factor involved in fibrosis. AIF-1 has the ability to proliferate and migrate lung fibroblasts. In addition, macrophage dendritic cells knockdown the AIF-1 gene were co-cultured with T cells, it was revealed that T cell proliferation due to nonspecific antigen stimulation was suppressed. Thus, it is suggested that AIF-1 is involved in the pathogenesis of acute and chronic stages of pulmonary fibrosis.

Academic Significance and Societal Importance of the Research Achievements

肺線維化の免疫反応を含めたメカニズムは未だ不明であり、リウマチ性疾患合併症として間質性肺炎から生じる肺線維症有効な治療法がなく難治性であり、生命予後を悪化させる。近年、AIF-1は、ヒトの全身性硬化症の間質性肺病変や線維化皮膚病変での発現がみられているが、繊維化に関わる機序は明らかにされていなかった。本研究では、AIF-1が、マクロファージや肺線維芽細胞からサイトカインやケモカインを誘導し、線維化に関与する増殖因子であるTGF-βを分泌することにより、肺の線維化の病因に深く関与する事が明らかになり、肺線維化治療の新たなターゲット分子になる可能性を示した。

Report

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

    (4 results)

All 2018 2017

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

  • [Journal Article] Role of allograft inflammatory factor-1 in bleomycin-induced lung fibrosis2018

    • Author(s)
      Hidetake Nagahara, Takahiro Seno, Aihiro Yamamoto, Hiroshi Obayashi, Takuya Inoue, Takashi Kida, Amane Nakabayashi, Yuji Kukida, Kazuki Fujioka, Wataru Fujii, Ken Murakami, Masataka Kohno, Yutaka Kawahito.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495(2) Issue: 2 Pages: 1901-1907

    • DOI

      10.1016/j.bbrc.2017.12.035

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ブレオマイシン誘導肺線維症におけるAIF-1の役割.2018

    • Author(s)
      永原秀剛, 妹尾高宏, 井上拓也, 木田 節, 中林 周, 茎田祐司, 藤岡数記, 和田 誠, 河野正孝, 川人 豊.
    • Organizer
      第62回日本リウマチ学会総会・学術集会.
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウスブレオマイシン誘導肺線維症におけるAIF-1の役割2017

    • Author(s)
      永原秀剛、妹尾高宏、井上拓也、木田節、中林周、茎田祐司、藤岡数記、和田誠、河野正孝、川人豊
    • Organizer
      第61回日本リウマチ学会総会・学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2017-04-20
    • Related Report
      2016 Research-status Report
  • [Presentation] マウスブレオマイシン誘導肺線維症におけるAIF-1の役割.2017

    • Author(s)
      永原秀剛, 妹尾高宏, 井上拓也, 木田 節, 中林 周, 茎田祐司, 藤岡数記, 和田 誠, 河野正孝, 川人 豊.
    • Organizer
      第61回日本リウマチ学会総会・学術集会.
    • Related Report
      2017 Research-status Report

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

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