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Analysis of anti-viral innate immunity and therapeutic strategies for upper respiratory disease.

Research Project

Project/Area Number 26293370
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionSapporo Medical University

Principal Investigator

Himi Tetsuo  札幌医科大学, 医学部, 教授 (90181114)

Co-Investigator(Kenkyū-buntansha) 横田 伸一  札幌医科大学, 医学部, 教授 (10325863)
高野 賢一  札幌医科大学, 医学部, 准教授 (70404689)
小笠原 徳子  札幌医科大学, 医学部, 助教 (00438061)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords上気道感染 / ウイルス / RSウイルス / インターフェロン / IRF3 / 気道上皮細胞 / 上気道 / ウイルス感染 / Ⅲ型インターフェロン / マクロライド / ストレス顆粒 / 抗ウイルス活性 / 鼻粘膜 / 上皮細胞 / 鼻粘膜上皮 / 抗ウイルス作用物質 / ムンプスウイルス / 麻疹ウイルス / ウイルス受容体 / RSウイルス / .インターフェロン / 呼吸器ウイルス / λインターフェロン / ウイルス持続感染
Outline of Final Research Achievements

We examined the effect of CAM on production of cytokines, CAM significantly suppressed RSV-induced production of IFN-λ1, λ2 and λ3. CAM dramatically suppressed RSV-induced promoter activity, 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.
In conclusion, 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. NIP-SNAP and MuV-induced SGs partly suppressed viral-induced type Ⅲ IFN production and suppressed the production of pro-inflammatory cytokines.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (32 results)

All 2018 2017 2016 2015 2014

All Journal Article (28 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 20 results,  Open Access: 11 results,  Acknowledgement Compliant: 9 results) Presentation (4 results)

  • [Journal Article] Evaluation of consistency in quantification of gene copy number by real-time reverse transcription quantitative polymerase chain reaction and virus titer by plaque-forming assay for human respiratory syncytial virus.2018

    • Author(s)
      Yamamoto K, Ogasawara N, Yamamoto S, Takano K, Shiraishi T, Sato T, Tsutsumi H, Himi T, Yokota SI.
    • Journal Title

      Microbiol Immunol.

      Volume: 62 Issue: 2 Pages: 90-98

    • DOI

      10.1111/1348-0421.12563

    • NAID

      40021481337

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of transcriptional factor p63 in regulation of epithelial barrier and ciliogenesis of human nasal epithelial cells2017

    • Author(s)
      Kaneko Yakuto、Kohno Takayuki、Kakuki Takuya、Takano Ken-ichi、Ogasawara Noriko、Miyata Ryo、Kikuchi Shin、Konno Takumi、Ohkuni Tsuyoshi、Yajima Ryoto、Kakiuchi Akito、Yokota Shin-ichi、Himi Tetsuo、Kojima Takashi
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 10935-10935

    • DOI

      10.1038/s41598-017-11481-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of claudin-4 via p63 in human epithelial cells.2017

    • Author(s)
      Kojima T, Kohno T, Kubo T, Kaneko Y, Kakuki T, Kakiuchi A, Kurose M, Takano KI, Ogasawara N, Obata K, Nomura K, Miyata R, Konno T, Ichimiya S, Himi T.
    • Journal Title

      Ann N Y Acad Sci.

      Volume: 1405 Issue: 1 Pages: 25-31

    • DOI

      10.1111/nyas.13456

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial proteins NIP-SNAP-1 and -2 are a target for the immunomodulatory activity of clarithromycin, which involves NF-κB-mediated cytokine production.2017

    • Author(s)
      Yamamoto S, Ogasawara N, Yamamoto K, Uemura C, Takaya Y, Shiraishi T, Sato T, Hashimoto S, Tsutsumi H, Takano K, Himi T, Yokota SI.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 483 Issue: 3 Pages: 911-916

    • DOI

      10.1016/j.bbrc.2016.12.133

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial proteins NIP-SNAP-1 and -2 are a target for the immunomodulatory activity of clarithromycin, which involves NF-κB-mediated cytokine production.2017

    • Author(s)
      Yamamoto S, Ogasawara N, Yamamoto K, Uemura C, Takaya Y, Shiraishi T, Sato T, Hashimoto S, Tsutsumi H, Takano K, Himi T, Yokota SI.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 483 Issue: 3 Pages: 911-916

    • DOI

      10.1016/j.bbrc.2016.12.100

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] HIV-associated cystic lesions of the parotid gland.2017

    • Author(s)
      Ogasawara N, Takano KI, Kobayashi H, Kikuchi K, Matsumiya H, Yoshioka I, Himi T.
    • Journal Title

      Auris Nasus Larynx.

      Volume: 44 Issue: 1 Pages: 126-130

    • DOI

      10.1016/j.anl.2016.05.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates2017

    • Author(s)
      Ohkoshi Y, Sato T, Suzuki Y, Yamamoto S, Shiraishi T, Ogasawara N, Yokota SI
    • Journal Title

      BioMed Research International

      Volume: Article ID 5470241 Pages: 5470241-5470241

    • DOI

      10.1155/2017/5470241

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone- Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4- ST131-H30R and O1-ST6482017

    • Author(s)
      Sato T, Suzuki Y, Shiraishi T, Honda H, Shinagawa M, Yamamoto S, Ogasawara N, Takahashi H, Takahashi S, Tamura Y, Yokota SI
    • Journal Title

      Antimicrob Agents Chemother

      Volume: 61 Issue: 2

    • DOI

      10.1128/aac.01654-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.2016

    • Author(s)
      Hashimoto S, Yamamoto S, Ogasawara N, Sato T, Yamamoto K, Katoh H, Kubota T, Shiraishi T, Kojima T, Himi T, Tsutsumi H, Yokota S
    • Journal Title

      PLoS One.

      Volume: Aug 4;3: Issue: 8 Pages: 16023-16023

    • DOI

      10.1371/journal.pone.0161793

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clarithromycin prevents human respiratory syncytial virus-induced airway epithelial responses by modulating activation of interferon regulatory factor-3.2016

    • Author(s)
      Yamamoto K, Yamamoto S, Ogasawara N, Takano K, Shiraishi T, Sato T, Miyata R, Kakuki T, Kamekura R, Kojima T, Tsutsumi H, Himi T, Yokota S.
    • Journal Title

      Pharmacol Res

      Volume: 111 Pages: 804-814

    • DOI

      10.1016/j.phrs.2016.07.033

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Adenovirus-Mediated ICOSIg Gene Therapy in a Presensitized Murine Model of Allergic Rhinitis.2016

    • Author(s)
      Sato J, Konno N, Murakami M, Uede T, Himi T.
    • Journal Title

      Adv Otorhinolaryngol.

      Volume: 77 Pages: 59-66

    • DOI

      10.1159/000441876

    • ISBN
      9783318056501, 9783318056518
    • Related Report
      2016 Annual Research Report
  • [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 S.
    • Journal Title

      Viral Immunol.

      Volume: 29 Issue: 5 Pages: 296-306

    • DOI

      10.1089/vim.2016.0004

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 上気道炎症と上皮バリア機能2016

    • Author(s)
      高野賢一,氷見徹夫
    • Journal Title

      別冊Bio Clinica:慢性炎症と疾患

      Volume: 5 Pages: 1-4

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 耳鼻咽喉科が依頼におけるインフルエンザに対するアプローチ2016

    • Author(s)
      高野賢一
    • Journal Title

      ENTONI

      Volume: 192 Pages: 189-194

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 微生物学的検査のピットフォール 的確な感染症診断 耳鼻咽喉科領域における結核菌感染症2016

    • Author(s)
      小笠原 徳子, 高野 賢一, 氷見 徹夫
    • Journal Title

      日本耳鼻咽喉科感染症・エアロゾル学会会誌

      Volume: 4 Pages: 77-81

    • NAID

      130007896187

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 抗菌薬耐性菌の驚くべき進化と脅威2016

    • Author(s)
      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: 4 Pages: 7-13

    • NAID

      130007896194

    • Related Report
      2016 Annual Research Report
  • [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

    • Related Report
      2015 Annual Research Report
    • 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

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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: 3 Pages: 1-8

    • Related Report
      2015 Annual Research Report
    • 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

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Leukotriene E<sub>4</sub> induces MUC5AC release from human airway epithelial NCI-H292 cells2015

    • Author(s)
      Shirasaki H, Kanaizumi E, Seki N, Himi T.
    • Journal Title

      Allergology International

      Volume: 64 Issue: 2 Pages: 169-174

    • DOI

      10.1016/j.alit.2014.11.002

    • NAID

      130005290288

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma2015

    • Author(s)
      Kamekura R, Shigehara K, Miyajima S, Jitsukawa S, Kawata K, Yamashita K, Nagaya T, Kumagai A, Sato A, Matsumiya H, Ogasawara N, Seki N, Takano K, Kokai Y, Takahashi H, Himi T, Ichimiya S
    • Journal Title

      Clinical Immunology

      Volume: in press Issue: 2 Pages: 120-5

    • DOI

      10.1016/j.clim.2015.02.016

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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

    • Related Report
      2014 Annual Research Report
    • Open Access
  • [Journal Article] 耳鼻咽喉科とウイルス  上気道粘膜とウイルス感染2014

    • Author(s)
      氷見徹夫, 高野 賢一, 大國 毅, 小笠原 徳子, 山本 圭佑, 高橋 希
    • Journal Title

      JOHNS

      Volume: 30 Pages: 1533-39

    • Related Report
      2014 Annual Research Report
  • [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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells2014

    • Author(s)
      Nomura K, Takano K, Himi T, Kojima T. (10名, 9, 10番)
    • Journal Title

      Respir Res

      Volume: 18 Issue: 1 Pages: 15-21

    • DOI

      10.1186/1465-9921-15-21

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 鼻粘膜とウイルス感染2014

    • Author(s)
      氷見徹夫.柏木征三郎
    • Journal Title

      インフルエンザ

      Volume: 15 Pages: 9-15

    • Related Report
      2014 Annual Research Report
  • [Presentation] クラリスロマイシンは軌道上秀RSVによって誘導されるインターフェロンをIRF-3を介して調節する2017

    • Author(s)
      山本 圭佑, 高野 賢一, 小笠原 徳子, 黒瀬 誠, 野村 一顕, 宮田 遼, 角木 拓也, 氷見 徹夫
    • Organizer
      第118回日本耳鼻咽喉科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Clarisromysin regulates production or induction of IFN and proinflammatory cytokine production by RSV infection in human airway epithelial cells via modulation nuclear translocation of IRF-3.2016

    • Author(s)
      Yamamoto K, Yamamoto S, Ogasawara N, Takano K, Ohkuni T, Kojima T, Tsutsumi H, Yokota S, Himi T
    • Organizer
      第64回日本ウイルス学会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Clarithromycin and garenoxacin supress proinflammatory cytokine and chemokane induction in airway epithelial cells induced by human RSV. via different signal pathway.2015

    • Author(s)
      Yamamoto K, Hashimoto S, Himi T et al
    • Organizer
      第63回日本ウイルス学会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2015-11-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト気道上皮細胞におけるRSウイルス感染によるサイトカイン産生誘導と抗生剤による阻害効果の検討2014

    • Author(s)
      山本 圭佑, 高野 賢一, 小笠原 徳子, 黒瀬 誠, 野村 一顕, 宮田 遼, 角木 拓也, 氷見 徹夫
    • Organizer
      日本鼻科学会
    • Place of Presentation
      大阪コングレコンベンションセンター
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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