Innate immune responses and chronic inflammatory lung diseases

• Project/Area Number: 25293192
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kagoshima University
• Principal Investigator: Inoue Hiromasa 鹿児島大学, 医歯学域医学系, 教授 (30264039)
• Co-Investigator(Kenkyū-buntansha): YAMASAKI Sho 九州大学, 生体医学研究所, 教授 (40312946) ; INOSHIMA Ichiro 九州大学, 医学研究院, 助教 (90380419) ; SAMUKAWA Takuya 鹿児島大学, 医歯学域医学部・歯学部附属病院, 助教 (10363623)
• Co-Investigator(Renkei-kenkyūsha): MARUYAMA Ikuro 鹿児島大学, 医歯学総合研究科, 特任教授 (20082282) ; KUBO Masato 東京理科大学, 生命医科学研究所, 教授 (40277281)
• Research Collaborator: WATANABE Masaki 鹿児島大学, 医歯学総合研究科, 特任助教 (90398298)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2013: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: 自然免疫 / 呼吸器 / 炎症性肺疾患 / 膠原病関連間質性肺炎 / ホスホリパーゼA2 / miRNA / 獲得免疫

Outline of Final Research Achievements

We studied the role of innate immune responses and its interaction with adaptive immune pathways in chronic inflammatory lung diseases and chronic pulmonary infections.
We found that high mobility group box 1 (HMGB1), one of the damage-associated molecular patterns, is released into the extracellular space during the early stage of an animal model of pulmonary arterial hypertension and contributes to the development of pulmonary arterial hypertension. Dectin-2 contributes to host immunity against mycobacterial infection through the recognition of mannose-capped lipoarabinomannan. Serum B cell activating factor (BAFF) levels were higher in the patients with connective tissue diseases-associated interstitial lung diseases compared to healthy subjects and the patients with idiopathic pulmonary fibrosis or idiopathic nonspecific interstitial pneumonia.

Research Products

• [Journal Article] Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma. (2016)
  • Author(s): Mizuno K, Seki N, Mataki H, Matsushita R, Kamikawaji K, Kumamoto T, Takagi K, Goto Y, Nishikawa R, Kato M, Enokida H, Nakagawa M, Inoue H.
  • Journal Title: Int J Oncol Volume: 48 Issue: 2 Pages: 450-450
  • DOI: 10.3892/ijo.2015.3289
  • Peer Reviewed / Open Access
• [Journal Article] Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease. (2015)
  • Author(s): Hamada T, Samukawa T, Kumamoto T, Hatanaka K, Tsukuya G, Yamamoto M, Machida K, Watanabe M, Mizuno K, Higashimoto I, Inoue Y, Inoue H.
  • Journal Title: BMC Pulm Med Volume: 15 Issue: 1 Pages: 110-110
  • DOI: 10.1186/s12890-015-0105-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An inhaled phosphodiesterase 4 inhibitor E6005 suppresses pulmonary inflammation in mice (2015)
  • Author(s): Kubota S, Watanabe M, Shirato M, Okuno T, Higashimoto I, Machida K, Yokomizo T, Inoue H
  • Journal Title: Eur J Pharmacol Volume: 768 Pages: 41-48
  • DOI: 10.1016/j.ejphar.2015.10.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Validation of a COPD screening questionnaire and establishment of diagnostic cut-points in a Japanese general population: The Hisayama study (2015)
  • Author(s): Tsukuya G, Matsumoto K, Fukuyama S, Crawford B, Nakanishi Y, Ichinose M, Machida K, Samukawa1 T, Ninomiya T, Kiyohara Y, Inoue H
  • Journal Title: Allergology International Volume: 64 Issue: 1 Pages: 49-53
  • DOI: 10.1016/j.alit.2014.06.002
  • NAID: 130004873118
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prevalence of asthma with airflow limitation, COPD, and COPD with variable airflow limitation in older subjects in a general Japanese population: The Hisayama Study (2015)
  • Author(s): Matsumoto K, Seki N, Fukuyama S, Moriwaki A, Kan-O K, Matsunaga Y, Noda N, Yoshida M, Koto H, Takata S, Nakanishi Y, Kiyohara Y, Inoue H
  • Journal Title: Respir Investig Volume: 53 Issue: 1 Pages: 22-29
  • DOI: 10.1016/j.resinv.2014.08.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma (2015)
  • Author(s): Mataki H, Seki N, Chiyomaru T, Enokida H, Goto Y, Kumamoto T, Machida K, Mizuno K, Nakagawa M, Inoue H.
  • Journal Title: International Journal of Oncology Volume: 46 Issue: 3 Pages: 1039-1050
  • DOI: 10.3892/ijo.2014.2802
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C (2015)
  • Author(s): Mataki H, Enokida H, Chiyomaru T, Mizuno K, Matsushita R, Goto Y, Nishikawa R, Higashimoto I, Samukawa T, Nakagawa M, Inoue H, Seki N.
  • Journal Title: Journal of Human Genetics Volume: 60 Issue: 2 Pages: 53-61
  • DOI: 10.1038/jhg.2014.111
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] HMGB1 promotes the development of pulmonary arterial hypertension in rats. (2014)
  • Author(s): Sadamura-Takenaka Y, Ito T, Noma S, Oyama Y, Yamada S, Kawahara K, Inoue H, Maruyama I.
  • Journal Title: PLoS One. Volume: 9 Issue: 7 Pages: e102482-e102482
  • DOI: 10.1371/journal.pone.0102482
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. (2014)
  • Author(s): Yonekawa A, Saijo S, Hoshino Y, Miyake Y, Ishikawa E, Suzukawa M, Inoue H, Tanaka M, Yoneyama M, Oh-Hora M, Akashi K, Yamasaki S.
  • Journal Title: Immunity Volume: 41 Issue: 3 Pages: 402-13
  • DOI: 10.1016/j.immuni.2014.08.005
  • Peer Reviewed / Open Access
• [Journal Article] Viral infection in asthma and COPD (2014)
  • Author(s): Matsumoto K, Inoue H
  • Journal Title: Respir Invest Volume: 52 Issue: 2 Pages: 92-100
  • DOI: 10.1016/j.resinv.2013.08.005
  • Peer Reviewed
• [Journal Article] Ａ turn on and a turn off: BLT1 and BLT2 mechanisms in the lung (2014)
  • Author(s): 渡辺正樹、井上博雅ほか
  • Journal Title: Expert Rev Respir Med Volume: 8 Issue: 4 Pages: 381-383
  • DOI: 10.1586/17476348.2014.908715
  • Peer Reviewed / Open Access
• [Presentation] 喘息とCOPDのオーバーラップ症候群(ACOS) (2015)
  • Author(s): 井上博雅
  • Organizer: 第25回日本呼吸ケア・リハビリテーション学会学術集会
  • Place of Presentation: 千葉県浦安市
  • Year and Date: 2015-10-15
  • Invited
• [Presentation] Tumor-suppressive microRNA-29s modulate oncogenic signaling pathways in lung squamous cell carcinoma (2015)
  • Author(s): Mataki H, Seki N, Enokida H, Mizuno K, Matsushita R, Nakagawa M, Hiromasa Inoue H.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2015-10-08
• [Presentation] Asthma-COPD Overlap Syndrome (ACOS)へのアプローチ (2015)
  • Author(s): 井上博雅
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京都千代田区
  • Year and Date: 2015-04-17
  • Invited
• [Presentation] シンポジウム 「COPDの啓蒙にむけて」早期治療の有用性 (2014)
  • Author(s): 井上博雅
  • Organizer: 第24回日本呼吸ケア・リハビリテーション学会学術集会
  • Place of Presentation: 奈良市（なら100年会館）
  • Year and Date: 2014-10-24 – 2014-10-25
• [Presentation] シンポジウム「創薬を視野に入れた呼吸器疾患の病態解明」COPDの創薬ターゲット (2014)
  • Author(s): 井上博雅
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪市（大阪国際会議場・リーガロイヤルホテル大阪）
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] Elevation of serum napsinA levels in patients with hypersensitive pneumonia (2013)
  • Author(s): T. Kumamoto, A. Harumatsu, K. Sakaue, T. Hamada, M. Yamamoto, T. Hamasaki, K. Mizuno, I. Higashimoto, T. Samukawa, H. Inoue
  • Organizer: European Respiratory Society Annual Congress 2013
  • Place of Presentation: Barcelona（Spain）
• [Presentation] B cell activating factor belonging to the TNF family might be a useful biomarker in interstitial lung diseases associated with connective tissue diseases (2013)
  • Author(s): T. Hamada, T. Kumamoto, A. Harumatsu, K. Mizuno, T. Samukawa, I. Higashimoto, M. Watanabe, H. Inoue
  • Organizer: European Respiratory Society Annual Congress 2013
  • Place of Presentation: Barcelona（Spain）