Role of IL-17A in the development of COPD exacerbation

• Project/Area Number: 17K16042
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: MATSUZAKI HIROTAKA 東京大学, 医学部附属病院, 特任助教 (00782187)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: IL-17A / COPD / exacerbation / adam10 / adam17 / COPD急性増悪 / ADAM10 / ADAM17 / poly(I:C) / エラスターゼ / CSE / 感染症

Outline of Final Research Achievements

It has been suggeted that IL-17A is involved in the development of neutrophilc inflammation and emphysema; however, the role of IL-17A in the development of COPD exacerbation remains to be clarified. We developed COPD and exacerbation mice model.Wild type mice and IL-17A KO mice were evaluated in these mice model.
In exacerbation mice model, airway inflammation was attenuated in IL-17A KO mice .The finding suggested that IL-17A is involved in the deveploment of COPD exacerbation.Then, we evaluated the defference of gene expression in viral infection model between wild type mice and IL-17A KO mice. As a result, Adam10 and Adam17 were focused.The analysis of mRNA expression in whold lung suggeted that the expression of Adam10 and Adam17 varied in COPD and exacerbation mice model under the effect of IL-17A.

Academic Significance and Societal Importance of the Research Achievements

ウイルス感染を主因とするCOPD急性増悪におけるIL-17Aの関与や機序は未解明な事が多い。本研究の結果から、マウスモデルにおいて急性増悪の気道炎症にIL-17Aが関与する可能性が示唆された。さらに上述したRNA-seq解析から気道炎症や気腫化に対する治療標的分子として注目を集めるADAM 10及びADAM17の2つの分子に着目した。両分子の急性増悪における病態への関与は未解明な事が多い。COPDや急性増悪モデルにおいてmRNAの発現変動を認めた事、その発現変動にIL-17Aの関与が示唆された事はADAM10及びADAM17両分子に新たな知見をもたらすものと考え、今後のさらなる研究が望まれる。

Research Products

• [Journal Article] CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts (2019)
  • Author(s): Takeshima Hideyuki、Horie Masafumi、Mikami Yu、Makita Kosuke、Miyashita Naoya、Matsuzaki Hirotaka、Noguchi Satoshi、Urushiyama Hirokazu、Hiraishi Yoshihisa、Mitani Akihisa、Borok Zea、Nagase Takahide、Yamauchi Yasuhiro
  • Journal Title: Allergology International Volume: 68 Issue: 1 Pages: 101-109
  • DOI: 10.1016/j.alit.2018.08.005
  • NAID: 130007557853
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice. (2019)
  • Author(s): Urushiyama H, Terasaki Y, Nagasaka S, Kokuho N, Endo Y, Terasaki M, Kunugi S, Makita K, Isago H, Hosoki K, Souma K, Ishii T, Matsuzaki H, Hiraishi Y, Mikami Y, Noguchi S, Tamiya H, Mitani A, Yamauchi Y, Shimizu A, Nagase T.
  • Journal Title: J Cell Mol Med. Volume: 3 Issue: 5 Pages: 1-9
  • DOI: 10.1111/jcmm.14255
  • Peer Reviewed / Open Access
• [Journal Article] Mechanism of Periostin Production in Human Bronchial Smooth Muscle Cells. (2018)
  • Author(s): Makita K, Mikami Y, Matsuzaki H, Miyashita N, Takeshima H, Noguchi S, Horie M, Urushiyama H, Iikura M, Hojo M, Nagase T, Yamauchi Y.
  • Journal Title: Int Arch Allergy Immunol Volume: 175 Issue: 1-2 Pages: 26-35
  • DOI: 10.1159/000485892
  • Peer Reviewed
• [Journal Article] Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC (2017)
  • Author(s): Horie M, Kaczkowski B, Ohshima M, Matsuzaki H, Noguchi S, Mikami Y, Lizio M, Itoh M, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest ARR, Takai D, Yamaguchi Y, Micke P, Saito A, Nagase T.
  • Journal Title: Mol Cancer Res. Volume: 15 Issue: 10 Pages: 1354-1365
  • DOI: 10.1158/1541-7786.mcr-17-0191
  • Peer Reviewed / Open Access / Int'l Joint Research