Investigation of the anti-viral mechanism by interference between lambda interferon subtypes

• Project/Area Number: 26670746
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Sapporo Medical University
• Principal Investigator: Himi Tetsuo 札幌医科大学, 医学部, 教授 (90181114)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ＲＳウイルス / インターフェロン / ＩＲＦ３ / 鼻粘膜 / 上皮細胞 / クラリスロマイシン / サイトカイン / .上気道感染 / Ⅲ型インターフェロン / 抗ウイルス作用 / ストレス顆粒 / ムンプスウイルス / ウイルス感染 / microRNA / ウイルス持続感染

Outline of Final Research Achievements

Human respiratory syncytial virus (RSV) infects to airway epithelium cells, and causes frequently bronchiolitis and pneumonia in infants. Clarithromycin (CAM), which is a one of the macrolide antimicrobial agents, is also known as an immunomodulator, and has been used for otitis media with effusion and chronic sinusitis.CAM suppresses the production of pro-inflammatory cytokines and IFNs induced by virus-related stimuli, such as RSV and poly I:C. CAM exerts these effects by inhibiting the dimerization and subsequent nuclear translocation of IRF3 in airway epithelial cells.
CAM also dramatically suppressed RSV-induced promoter activity of the PRDIII-I, which is an IRF3 biding element. RSV-induced phosphorylation of IRF-3 did not alter in the presence of CAM. CAM inhibits IRF3 dimerization and its subsequent nuclear translocation from cytosol upon stimulation with poly I:C or RSV.

Research Products

• [Journal Article] Measles Virus Genotype D Wild Strains Suppress Interferon-Stimulated Gene Expression More Potently than Laboratory Strains in SiHa Cells. (2016)
  • Author(s): Jinushi M, Yamamoto S, Ogasawara N, Nagano H, Hashimoto S, Tsutsumi H, Himi T, Yokota SI.
  • Journal Title: Viral Immunol. Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium. (2016)
  • Author(s): Abe A, Takano K, Kojima T, Nomura K, Kakuki T, Kaneko Y, Yamamoto M, Takahashi H, Himi T.
  • Journal Title: J Mol Histol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Claudin-binder C-CPE mutants enhance permeability of insulin across human nasal epithelial cells. (2015)
  • Author(s): Kojima T, Kondoh M, Keira T, Takano KI, Kakuki T, Kaneko Y, Miyata R, Nomura K, Obata K, Kohno T, Konno T, Sawada N, Himi T.
  • Journal Title: Drug Deliv. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Poly(I:C) induced microRNA-146a regulates epithelial barrier and secretion of proinflammatory cytokines in human nasal epithelial cells. (2015)
  • Author(s): Miyata R, Kakuki T, Nomura K, Ohkuni T, Ogasawara N, Takano K, Konno T, Kohno T, Sawada N, Himi T, Kojima T.
  • Journal Title: Eur J Pharmacol. Volume: 761 Pages: 375-382
  • DOI: 10.1016/j.ejphar.2015.04.031
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Isogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells. (2014)
  • Author(s): Miyata R, Nomura K, Kakuki T, Takano K, Kohno T, Konno T, Sawada N, Himi T, Kojima T.
  • Journal Title: J Membr Biol. Volume: 248(2) Issue: 2 Pages: 327-336
  • DOI: 10.1007/s00232-015-9774-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ΔNp63 controls a TLR3-mediated mechanism that abundantly provides thymic stromal lymphopoietin in atopic dermatitis. (2014)
  • Author(s): Kubo T, Kamekura R, Kumagai A, Kawata K, Yamashita K, Mitsuhashi Y, Kojima T, Sugimoto K, Yoneta A, Sumikawa Y, Yamashita T, Sato N, Himi T, Ichimiya S
  • Journal Title: PLoS One Volume: 9(8) Issue: 8 Pages: e105498-e105498
  • DOI: 10.1371/journal.pone.0105498
  • Peer Reviewed / Open Access
• [Journal Article] 鼻粘膜上皮におけるRSウイルス感染メカニズムと新たな予防戦略 (2014)
  • Author(s): 高野賢一，氷見徹夫
  • Journal Title: 日本鼻科学会会誌 Volume: 53 Pages: 36-38
  • NAID: 130004546200
  • Peer Reviewed
• [Journal Article] RSウイルス感染症に対するマクロライドの可能性 (2014)
  • Author(s): 横田伸一，堤裕幸，氷見徹夫
  • Journal Title: The Japanese Journal of Antibiotics Volume: 67 Pages: 147-155
  • NAID: 40020132040
• [Journal Article] ウイルス性炎症における上気道粘膜の役割 鼻粘膜上皮機能解析から炎症制御戦略を探る (2014)
  • Author(s): 氷見 徹夫, 高野 賢一, 大國 毅, 小笠原 徳子, 正木 智之, 小幡 和史, 堤 裕幸, 小島 隆, 澤田 典均, 横田 伸一
  • Journal Title: 日本耳鼻咽喉科感染症・エアロゾル学会会誌 Volume: 2 Pages: 1-5
  • NAID: 130007930871