Roles of new cytokine IL-38 in inflammatory diseases

• Project/Area Number: 25461202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kurume University
• Principal Investigator: Hoshino Tomoaki 久留米大学, 医学部, 教授 (00261066)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症 / サイトカイン / IL-38 / 呼吸器疾患

Outline of Final Research Achievements

We generated anti-human IL-38 monoclonal antibodies in order to perform immunohistochemical staining and an enzyme-linked immunosorbent assay. While human recombinant IL-38 protein was not cleaved by recombinant caspase-1, chymase, and PR3 in vitro, IL-38 cDNA-overexpression produced a soluble form of IL-38 protein. Furthermore, immunohistochemical analysis showed that synovial tissues obtained from RA patients strongly expressed IL-38 protein. To investigate the biological role of IL-38, C57BL/6 IL-38 gene deficient (-/-) mice were used in an autoantibody-induced rheumatoid arthritis (RA) mouse model. In IL-38 (-/-) mouse, we observed a worse disease severity that was accompanied by higher IL-1beta and IL-6 gene expression in the joints as compared to control mice. Therefore, IL-38 acts as an inhibitor of the pathogenesis of autoantibody-induced arthritis in mice and may have a role in the development or progression of human RA (Biochemistry and Biophysics Reports 2015).

Research Products

• [Journal Article] IL-38: A new factor in rheumatoid arthritis (2015)
  • Author(s): S-i Takenaka, S Kaieda, T Kawayama, M Matsuoka, Y Kaku, T Kinoshita, Y Sakazaki, M Okamoto, T Hoshino
  • Journal Title: Biochemistry and Biophysics Reports Volume: 4 Pages: 386-391
  • DOI: 10.1016/j.bbrep.2015.10.015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The progression of comorbidity in il-18 transgenic chronic obstructive pulmonary disease mice model. (2014)
  • Author(s): Takenaka S, Kawayama T 他
  • Journal Title: Biochem Biophys Res Commun Volume: 445 Issue: 3 Pages: 597-601
  • DOI: 10.1016/j.bbrc.2014.02.052
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13 (2013)
  • Author(s): Masanori Sawada, Haruki Imaoka et al.
  • Journal Title: PLoS ONE Volume: Vol. 8 Issue: 1 Pages: 54623-54623
  • DOI: 10.1371/journal.pone.0054623
  • Peer Reviewed
• [Presentation] 新規IL-1ファミリーサイトカインIL-38の膠原病疾患における発現および機能解析 (2016)
  • Author(s): 星野友昭
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-04-21