The role of claudins in the lung fibrosis post influenza virus-induced acute lung injury

• Project/Area Number: 25860825
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Tohoku University
• Principal Investigator: Aoyagi Tetsuji 東北大学, 医学(系)研究科(研究院), 講師 (50581609)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 急性肺傷害 / 繊維化 / Influenza virus / Lipopolysaccharides / Claudin / Microparticles / Lipopolysaccharide / インフルエンザウイルス / Tight-junction / 肺傷害 / 肺線維化 / Elastase

Outline of Final Research Achievements

The clinical course and pathophysiological feature of ARDS are characterized as three phases: acute exduative, proliferative and fibrotic. We investigated the role of claudins, a family of proteins in the components of the tight junction, in acute and fibrotic phase of lung injury. We induced nonviral ARDS by alpha-galactosylceramide(GalCer) and LPS and viral ARDS by influenza virus infection. Claudin-5 and -18 are expressed in naive lungs. In both ARDS model, expression of claudin-4 was elevated and claudin-18 mRNA decreased in acute phases of lung injury. Claudin-4 was expressed in not only epithelial cells but leukocytes recruited into the lungs. Micorparticles in BAL fluid after influenza virus infection was observed. Influenza virus induced MPs have a potential to induced the cytokines and chemokines in alveolar machrophasge. These results indicated that claudins may be involved in the pathogenesis of acute phase of lung injury.

Research Products

• [Journal Article] A case of culture-negative endocarditis due to Streptococcus tigurinus (2015)
  • Author(s): Kanamori H, Kakuta R, Yano H, Suzuki T, Gu Y, Oe C, Inomata S, Aoyagi T, Hatta M, Endo S, Tokuda K, Weber DJ, Nakamura Y, Saiki Y, Kaku M
  • Journal Title: J Infect Chemother Volume: 21 Issue: 2 Pages: 138-140
  • DOI: 10.1016/j.jiac.2014.08.014
  • Peer Reviewed
• [Journal Article] Helicobacter cinaedi causing infected abdominal aortic aneurysm (2014)
  • Author(s): Kakuta R, Yano H, Kanamori H, Shimizu T, Gu Y, Hatta M, Aoyagi T, Endo S, Inomata S, Oe C, Tokuda K, Ozawa D, Goto H, Katori Y, and Kaku M
  • Journal Title: Emerg Infect Dis Volume: 20 Issue: 11 Pages: 1942-1945
  • DOI: 10.3201/eid2011.140440
  • Peer Reviewed
• [Journal Article] Prevaccination antibody screening and immunization program for healthcare personnel against measles, mumps, rubella, and varicella in a Japanese tertiary care hospital. (2014)
  • Author(s): Kanamori H, Tokuda K, Ikeda S, Endo S, Ishizawa C, Hirai Y, Takahashi M, Aoyagi T, Hatta M, Gu Y, Yano H, Weber DJ, Kaku M.
  • Journal Title: Tohoku J Exp Med. Volume: 234 Pages: 111-116
  • NAID: 130004687565
  • Peer Reviewed
• [Journal Article] Impact of psm-mec in the Mobile Genetic Element on the Clinical Characteristics and Outcome of SCCmec-II Methicillin-resistant Staphylococcus aureus Bacteremia in Japan (2014)
  • Author(s): Aoyagi T, Kaito C, Sekimizu K, Omae Y, Saito Y, Mao H, Inomata S, Hatta M, Endo S, Kanamori H, Gu Y, Tokuda K, Yano H, Kitagawa M, Kaku M
  • Journal Title: Clin Microbiol Infect. Volume: 6 Mar
  • Peer Reviewed
• [Journal Article] Involvement of high mobility group box 1 and the therapeutic effect of recombinant thrombomodulin in a mouse model of severe acute respiratory distress syndrome (2013)
  • Author(s): Kudo D, Toyama M, Aoyagi T, Akahori Y, Yamamoto H, Ishii K, Kanno E, Maruyama R, Kaku M, Kushimoto S, Kawakami K
  • Journal Title: Clin Exp Immunol. Volume: 173 Pages: 276-87
  • Peer Reviewed
• [Journal Article] Low-dose interferon-α treatment improves survival and inflammatory responses in a mouse model of fulminant acute respiratory distress syndrome. (2013)
  • Author(s): Kudo D, Uno K, Aoyagi T, Akahori Y, Ishii K, Kanno E, Maruyama R, Kushimoto S, Kaku M, Kawakami K
  • Journal Title: Inflammation. Volume: 36 Pages: 812-20
  • Peer Reviewed
• [Presentation] IL-36R Blockade Attenuates Lung Injury and Mortality after H1N1 Influenza Virus Infection in Mice (2016)
  • Author(s): T Aoyagi, MW Newstead, X Zeng, M Kaku, TJ Standiford
  • Organizer: ATS 2016
  • Place of Presentation: San Fransisco, USA
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Distribution of the Ba813 gene among Bacillus cereus in the Hospital Setting (2015)
  • Author(s): T Aoyagi, M Kawauchi, Y Kishihara, K Tokuda, M Kaku
  • Organizer: ICAAC/ICC 2015
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] Improvement in lipopolysaccharide-induced fulminate acute respiratory distress syndrome model by etoposide plus steroid therapy (2014)
  • Author(s): T. Aoyagi, Y. Sato, K. Kawakami, M. Toyama, K. Ishii, H. Kanamori, S. Endo, M. Hatta, Y. Gu, K. Tokuda, H. Yano, M. Kaku
  • Organizer: American Thorasic Society 2014
  • Place of Presentation: San Diego, USA
• [Presentation] 炎症性単球をターゲットにした劇症型急性肺傷害実験動物モデルの治療 (2014)
  • Author(s): 青柳哲史，佐藤由紀夫，川上和義，河内美奈，金森 肇，遠藤史郎， 八田益充，具 芳明，徳田浩一，矢野寿一，賀来満夫
  • Organizer: 第88回日本感染症学会学術講演会 第62回日本化学療法学会総会 合同学会
  • Place of Presentation: 福岡県
• [Presentation] Association between psm-mec on the Mobile Genetic Element and Clinical Manifestation of Methicillin-Resistant Staphylococcus aureus Infection (2013)
  • Author(s): T. Aoyagi, None C. Kaito, None K. Sekimizu, None Y. Omae, None Y. Saito, None H. Mao, None S. Inomata, None S. Endo, None M. Hatta, None Y. Gu, None K. Tokuda, None H. Yano, None M. Kitagawa, None M. Kaku
  • Organizer: ID week 2013
  • Place of Presentation: San Francisco, USA