Functional analysis of CCL1 on development and exacerbation of interstitial pneumonia by SPC-CCL1 transgenic mice.

• Project/Area Number: 26461153
• 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: Yamagata University
• Principal Investigator: INOUE Sumito 山形大学, 医学部, 助教 (70466621)
• Co-Investigator(Renkei-kenkyūsha): SHIBATA Yoko 山形大学, 医学部, 講師 (60333978) ; ABE Shuichi 山形大学, 医学部, 非常勤講師 (40400543)
• Research Collaborator: IGARASHI Akira 山形大学, 医学部, 助教 (40637170)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 間質性肺炎 / ケモカイン / CCL-1 / 呼吸器 / CCL1 / 遺伝子改変マウス

Outline of Final Research Achievements

CCL1 transgenic mice (SPC-CCL1 Tg mice), overexpressing CCL1 specifically in the lungs were newly produced and examined in a BCG infection model. As a result, there was an increase in granuloma and suppression of interstitial inflammation in the lung in these mice. DNA microarray analysis revealed increased expression in 47 genes associated with "response to biological stress", Ern1 involved in endoplasmic reticulum stress and granulomatous formation, immunoglobulin related genes such as Ighg, IGHV, Igk-V5 expressions enhancement were observed. Enhancement of expression of Phospho-Ire1, an autophosphorylated form of Ire1 which is an Ern-1 encoded endoplasmic reticulum transmembrane kinase, was observed.

Research Products

• [Journal Article] Decreased left ventricular stroke volume is associated with low-grade exercise tolerance in patients with chronic obstructive pulmonary disease. (2017)
  • Author(s): Inoue S, Shibata Y, Kishi H, Nitobe J, Iwayama T, Yashiro Y, Nemoto T, Sato K, Sato M, Kimura T, Igarashi A, Tokairin Y, Kubota I.
  • Journal Title: BMJ Open Respir Res. Volume: 4 Issue: 1 Pages: e000158-e000158
  • DOI: 10.1136/bmjresp-2016-000158
  • Peer Reviewed / Open Access
• [Journal Article] MafB enhances the phagocytic activity of RAW264.7 macrophages by promoting Fcgr3 expression. (2017)
  • Author(s): Nemoto T, Shibata Y, Inoue S, Igarashi A, Tokairin Y, Yamauchi K, Kimura T, Sato M, Sato K, Nakano H, Abe S, Nishiwaki M, Kubota I.
  • Journal Title: Biochem Biophys Res Commun. Volume: 482 Issue: 2 Pages: 375-381
  • DOI: 10.1016/j.bbrc.2016.11.070
  • Peer Reviewed
• [Journal Article] Role of chemokine C-C motif ligand-1 in acute and chronic pulmonary inflammations. (2016)
  • Author(s): Kishi H, Sato M, Shibata Y, Sato K, Inoue S, Abe S, Kimura T, Nishiwaki M, Yamauchi K, Nemoto T, Igarashi A, Tokairin Y, Nakajima O, Kubota I.
  • Journal Title: Springerplus Volume: 5 Issue: 1 Pages: 1241-1241
  • DOI: 10.1186/s40064-016-2904-z
  • Peer Reviewed / Open Access
• [Journal Article] Predictors for mortality from respiratory failure in a general population. (2016)
  • Author(s): Kobayashi M, Shibata Y, Inoue S, Igarashi A, Sato K, Sato M, Nemoto T, Abe Y, Nunomiya K, Nishiwaki M, Tokairin Y, Kimura T, Daimon M, Makino N, Watanabe T, Konta T, Ueno Y, Kato T, Kayama T, Kubota I.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 26053-26053
  • DOI: 10.1038/srep26053
  • Peer Reviewed / Open Access
• [Journal Article] Low arterial blood oxygenation is associated with calcification of the coronary arteries in patients with chronic obstructive pulmonary disease. (2015)
  • Author(s): Inoue S, Shibata Y, Kishi H, Hasegawa H, Nitobe J, Iwayama T, Yashiro Y, Nemoto T, Sato K, Nakano H, Sato M, Nunomiya K, Aida Y, Yamauchi K, Igarashi A, Abe S, Kubota I.
  • Journal Title: Respir Investig Volume: 53 Issue: 3 Pages: 111-116
  • DOI: 10.1016/j.resinv.2015.01.002
  • Peer Reviewed
• [Journal Article] Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice. (2014)
  • Author(s): Aida Y, Shibata Y, Abe S, Inoue S, Kimura T, Igarashi A, Yamauchi K, Nunomiya K, Kishi H, Nemoto T, Sato M, Sato-Nishiwaki M, Nakano H, Sato K, Kubota I
  • Journal Title: Int J Biol Sci. Volume: 10 Issue: 8 Pages: 882-894
  • DOI: 10.7150/ijbs.8737
  • Peer Reviewed / Open Access
• [Journal Article] Association between plasma adiponectin levels and decline in forced expiratory volume in 1 s in a general Japanese population: the Takahata study. (2014)
  • Author(s): Sato K, Shibata Y, Abe S, Inoue S, Igarashi A, Yamauchi K, Aida Y, Nunomiya K, Nakano H, Sato M, Kimura T, Nemoto T, Watanabe T, Konta T, Ueno Y, Kato T, Kayama T, Kubota I.
  • Journal Title: Int J Med Sci. Volume: 11 Issue: 8 Pages: 758-764
  • DOI: 10.7150/ijms.8919
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between Serum Level of Lymphatic Vessel Endothelial Hyaluronan Receptor-1 and Prognosis in Patients with Lung Cancer (2013)
  • Author(s): Nunomiya K et al.
  • Journal Title: J. Cancer Volume: 5 Issue: 3 Pages: 242-247
  • DOI: 10.7150/jca.8486
  • Peer Reviewed / Open Access
• [Presentation] 山形高畠研究における呼吸機能と生命予後の関連 (2016)
  • Author(s): 井上純人
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-08
• [Presentation] マウス肺組織におけるFam13aの局在と発現の解析 (2016)
  • Author(s): 佐藤正道，柴田陽光，井上純人，五十嵐朗，東海林佳兼，根本貴子，佐藤建人，小林真紀，阿部祐紀，久保田功
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-08
• [Presentation] マウス肺組織におけるIreb2の局在と発現の検討 (2016)
  • Author(s): 佐藤正道，柴田陽光，井上純人，五十嵐朗，東海林佳兼，根本貴子，佐藤建人，小林真紀，阿部祐紀，久保田功
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-08
• [Presentation] 高齢者肺炎における血清鉄と予後の関係 (2016)
  • Author(s): 佐藤建人，阿部祐紀，佐藤正道，根本貴子，西脇道子，木村友美，山内啓子，五十嵐朗，東海林佳兼，井上純人，柴田陽光，久保田功
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-08
• [Presentation] 転写因子MafBのマクロファージ貪食能に与える影響の検討 (2016)
  • Author(s): 根本貴子，阿部祐紀，小林真紀，佐藤建人，佐藤正道，西脇道子，木村友美，山内啓子，五十嵐朗，東海林佳兼，井上純人，柴田陽光，久保田功
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-08
• [Presentation] COPD増悪入院患者の予後因子の検討 (2016)
  • Author(s): 佐藤正道，井上純人，五十嵐朗，東海林佳兼，根本貴子，佐藤建人，小林真紀，阿部祐紀，柴田陽光，久保田功
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-08
• [Presentation] 低鉄状態がLipopolysaccharide誘発急性肺障害に及ぼす影響についての検討 (2016)
  • Author(s): 佐藤建人，阿部祐紀，佐藤正道，根本貴子，西脇道子，木村友美，山内啓子，五十嵐朗，東海林佳兼，井上純人，柴田陽光，久保田功
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-08
• [Presentation] SPC- CCL1 Tgマウスにおける遺伝子発現および肉芽腫の形成の違い (2015)
  • Author(s): 佐藤正道、柴田陽光、岸宏幸、阿部修一、井上純人、五十嵐朗、木村友美、西脇道子、布宮慶子、根本貴子、佐藤建人、阿部祐紀、久保田功
  • Organizer: 第55回日本呼吸器学会総会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2015-04-17 – 2015-04-19
• [Presentation] The difference in the expression of Ern1 and the formation of granulomas in SPC-CCL1 Tg mice (2014)
  • Author(s): M. Sato, H. Kishi, S. Abe, S. Inoue, K. Sato, H. Nakano, T. Nemoto, K. Nunomiya, Y. Aida, T. Kimura, K. Yamauchi, A. Igarashi, I. Kubota, Y. Shibata
  • Organizer: American Thoracic Society 2014
  • Place of Presentation: サンディエゴコンベンションセンター（アメリカ合衆国）
  • Year and Date: 2014-05-16 – 2014-05-21