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Regulation of IL-18 and IL-38 for the treatment of inflammatory pulmonary diseases

Research Project

Project/Area Number 16K09595
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKurume University

Principal Investigator

Hoshino Tomoaki  久留米大学, 医学部, 教授 (00261066)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsIL-38 / 喘息 / 好酸球 / IL-5 / 炎症性肺疾患 / サイトカイン / IL-18 / 気管支喘息マウスモデル / 気管支喘息 / 分子細胞呼吸器学
Outline of Final Research Achievements

The role of IL-38, a new member of the IL-1 family, in airway eosinophilic inflammatory conditions such as asthma is unclear. To investigate the role of IL-38 in airway eosinophilic inflammation, an IL-38-gene deficient (KO) murine asthma model was analyzed. The IL-38 and IL-5 mRNA in WT mice was significantly higher after OVA challenge than after saline challenge (p<0.05). The number of airway eosinophils in IL-38-KO mice was significantly lower than in WT mice after OVA challenge (p<0.01). BALF analysis confirmed the lower number of airway eosinophils in IL-38-KO mice and showed that this was significantly associated with lower IL-5 protein levels (r=0.92, p<0.0001). However, the additional rm IL-38 protein did not neutralize airway eosinophilia in IL-38-KO mice.IL-38 may enhance airway eosinophilic inflammation in asthma through IL-5 induction.We also reported that IL-18 strongly involves in activation of Macrophage Activation Syndrome(MAS).

Academic Significance and Societal Importance of the Research Achievements

新規IL-1ファミリーサイトカインIL-38は抗炎症性サイトカインの可能性があることが示唆された(Biochemistry and Biophysics Reports 2015)。一方、IL-38は炎症性サイトカインの可能性を本研究で証明した。すなわち、IL-38は抗炎症性と炎症性サイトカインの二つの可能性を本研究で証明した。
申請者は抗ヒトIL-38モノクロナール抗体を樹立した。抗IL-38モノクロナール抗体H127CはBiolegend, eBioscienceから世界中で販売され,IL-38の研究に役立っている。

Report

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

    (8 results)

All 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 8 results,  Acknowledgement Compliant: 1 results)

  • [Journal Article] Association between soluble immune mediators and tumor responses in patients with nonsmall cell lung cancer treated with anti-PD-1 inhibitor.2019

    • Author(s)
      Matsuo N, Azuma K, Hattori S, Ohtake J, Kawahara A, Ishii H, Tokito T, Yamada K, Shibata Y, Shimokawaji T, Kondo T, Kato T, Saito H, Yamada K, Sasada T, Hoshino T.
    • Journal Title

      Int J Cancer.

      Volume: 144 Issue: 5 Pages: 1170-1179

    • DOI

      10.1002/ijc.31923

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Attenuated Airway Eosinophilic Inflammations in IL-38 Knockout Mouse Model2018

    • Author(s)
      MATSUOKA MASANOBU、KAWAYAMA TOMOTAKA、TOMINAGA MASAKI、KAIEDA SHINJIRO、TOKUNAGA YOSHIHISA、KAKU YOICHIRO、IMAOKA HARUKI、KINOSHITA TAKASHI、OKAMOTO MASAKI、AKIBA JUN、HOSHINO TOMOAKI
    • Journal Title

      The Kurume Medical Journal

      Volume: 65 Issue: 2 Pages: 37-46

    • DOI

      10.2739/kurumemedj.MS652009

    • NAID

      130007650022

    • ISSN
      0023-5679, 1881-2090
    • Year and Date
      2018-06-30
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome2018

    • Author(s)
      Weiss Eric S.、Girard-Guyonvarc’h Charlotte、Holzinger Dirk、de Jesus Adriana A.、Tariq Zeshan、Picarsic Jennifer、Schiffrin Eduardo J.、Foell Dirk、Grom Alexei A.、Ammann Sandra、Ehl Stephan、Hoshino Tomoaki、Goldbach-Mansky Raphaela、Gabay Cem、Canna Scott W.
    • Journal Title

      Blood

      Volume: 131 Issue: 13 Pages: 1442-1455

    • DOI

      10.1182/blood-2017-12-820852

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Il-33/st2 contributes to severe symptoms in plasmodium chabaudi-infected balb/c mice2017

    • Author(s)
      Seki T, Obata-Ninomiya K, Shimogawara-Furushima R, Arai T, Akao N, Hoshino T, Ohta N.
    • Journal Title

      Parasitology international

      Volume: 印刷中 Issue: 1 Pages: 64-69

    • DOI

      10.1016/j.parint.2017.03.008

    • Related Report
      2018 Annual Research Report 2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis2017

    • Author(s)
      Tominaga Masaki、Okamoto Masaki、Kawayama Tomotaka、Matsuoka Masanobu、Kaieda Shinjiro、Sakazaki Yuki、Kinoshita Takashi、Mori Daisuke、Inoue Akira、Hoshino Tomoaki
    • Journal Title

      Respiratory Investigation

      Volume: 55 Issue: 5 Pages: 293-299

    • DOI

      10.1016/j.resinv.2017.06.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma: Possible association with PD-L1 expression2017

    • Author(s)
      Takada Kazuki、Okamoto Tatsuro、Tominaga Masaki、Teraishi Koji、Akamine Takaki、Takamori Shinkichi、Katsura Masakazu、Toyokawa Gouji、Shoji Fumihiro、Okamoto Masaki、Oda Yoshinao、Hoshino Tomoaki、Maehara Yoshihiko
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 7 Pages: e0181598-e0181598

    • DOI

      10.1371/journal.pone.0181598

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease.2017

    • Author(s)
      Yoshida N, Okamoto M, Kaieda S, Fujimoto K, Ebata T, Tajiri M, Nakamura M, Tominaga M, Wakasugi D, Kawayama T, Kuwana M, Mimori T, Ida H, Hoshino T
    • Journal Title

      Respir Investig.

      Volume: 55(1) Issue: 1 Pages: 24-32

    • DOI

      10.1016/j.resinv.2016.08.007

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The usefulness of monomeric periostin as a biomarker for idiopathic pulmonary fibrosis2017

    • Author(s)
      Ohta S, Okamoto M, Fujimoto K, Sakamoto N, Takahashi K, Yamamoto H, Kushima H, Ishii H, Akasaka K, Ono J, Kamei A, Azuma Y, Matsumoto H, Yamaguchi Y, Aihara M, Johkoh T, Kawaguchi A, Ichiki M, Sagara H, Kadota JI, Hanaoka M, Hayashi SI, Kohno S, Hoshino T, Izuhara K
    • Journal Title

      PloS one

      Volume: 12 Issue: 3 Pages: e0174547-e0174547

    • DOI

      10.1371/journal.pone.0174547

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant

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

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