Analysis of the function of CCL1 during respiratory tract infection in C-C motif ligand-1 transgenic mouse

• Project/Area Number: 23591111
• 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)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 呼吸器 / 感染症 / 慢性閉塞性肺疾患 / 遺伝子改変マウス / 呼吸器感染症 / CCL1

Research Abstract

We generated the CCL1 (NCBI: rs2282691) transgenic mice using surfactant protein C promoter (SPC-CCL1 Tg), which overexpressed CCL1 gene in the lungs. We developed the Mycobacterium bovis Bacillus Calmette Guérin (BCG) infection models in SPC-CCL1 Tg mice.
Microscopic observation revealed that the numbers of granulomas in the lungs were significantly increased in SPC-CCL1 Tg mice. In DNA microarray analyses, 4,569 genes had 3 times and higher or one third and lower expression in the lung of Tg mice compare to that of WT mouse. Hierarchical cluster analysis of those genes revealed that Ern1, that plays important roles in endoplasmic reticulum stress and in granuloma formation, was more upregulated in the lung of BCG-treated SPC-CCL1 Tg mice compared to that of wild type mice.CCL1 overexpression increased the formation of granulomas upon BCG infection in the lungs. SPC-CCL1 Tg mice showed significant gene expression of Ern1 in comparison with wild type mice.

Research Products

• [Journal Article] Relationship between Serum Level of Lymphatic Vessel Endothelial Hyaluronan Receptor-1 and Prognosis in Patients with Lung Cancer (2014)
  • Author(s): Nunomiya K, Shibata Y, Abe S, Inoue S, Igarashi A, Yamauchi K, Kimura T, Aida Y, Nemoto T, Sato M, Kishi H, Nakano H, Sato K, Kubota I
  • Journal Title: J Cancer Volume: 5(3) Pages: 242-247
  • Peer Reviewed
• [Journal Article] A lower level of forced expiratory volume in 1 second is a risk factor for all-cause and cardiovascular mortality in a Japanese population : the Takahata study (2013)
  • Author(s): Shibata Y, Inoue S, Igarashi A, Yamauchi K, Abe S, Aida Y, Nunomiya K, Sato M, Nakano H, Sato K, Nemoto T, Kimura T, Watanabe T, Konta T, Daimon M, Ueno Y, Kato T, Kayama T, Kubota I
  • Journal Title: PLoS One Volume: 8(12)
  • Peer Reviewed
• [Journal Article] Relationships between values of antibodies to several connective tissue disease autoantigens and pulmonary function in a Japanese general population : the Takahata study (2013)
  • Author(s): Nakano H, Shibata Y, Inoue S, Igarashi A, Yamauchi K, Abe S, Sato M, Aida Y, Nunomiya K, Kimura T, Nemoto T, Watanabe T, Konta T, Ueno Y, Kato T, Kayama T, Kubota I
  • Journal Title: PLoS One Volume: 8(12)
  • Peer Reviewed
• [Journal Article] Relationship between Plasma Fibrinogen Levels and Pulmonary Function in the Japanese Population : The Takahata Study (2013)
  • Author(s): Shibata Y, Abe S, Inoue S, Igarashi A, Yamauchi K, Aida Y, Kishi H, Nunomiya K, Nakano H, Sato M, Sato K, Kimura T, Nemoto T, Watanabe T, Konta T, Ueno Y, Kato T, Kayama T, Kubota I
  • Journal Title: Int J Med Sci. Volume: 10(11) Pages: 1530-1536
  • Peer Reviewed
• [Journal Article] Elevated Serum Iron Is a Potent Biomarker for Spirometric Resistance to Cigarette Smoke among Japanese Males : The Takahata Study (2013)
  • Author(s): Shibata Y, Inoue S, Igarashi A, Yamauchi K, Abe S, Aida Y, Nunomiya K, Sato M, Nakano H, Sato K, Watanabe T, Konta T, Ueno Y, Kato T, Kayama T, Kubota I
  • Journal Title: PLoS One Volume: 8(9)
  • Peer Reviewed
• [Journal Article] Reduced Number and Morphofunctional Change of Alveolar Macrophages in MafB Gene-Targeted Mice (2013)
  • Author(s): Sato-Nishiwaki M, Aida Y, Abe S, Shibata Y, Kimura T, Yamauchi K, Kishi H, Igarashi A, Inoue S, Sato M, Nakajima O, Kubota I
  • Journal Title: PLoS One Volume: 8(9)
  • Peer Reviewed
• [Journal Article] Influence of corticosteroid therapy on the serum antibody response to influenza vaccine in elderly patients with chronic pulmonary diseases (2013)
  • Author(s): Inoue S, Shibata Y, Takabatake N, Igarashi A, Abe S, Kubota I
  • Journal Title: EXCLI Journal Volume: 12 Pages: 760-765
  • Peer Reviewed
• [Journal Article] Retrospective Analysis of the Relationship between Decline in FEV(1) and Abdominal Circumference in Male Smokers : the Takahata Study (2013)
  • Author(s): Sato M, Shibata Y, Abe S, Inoue S, Igarashi A, Yamauchi K, Aida Y, Kishi H, Nunomiya K, Nakano H, Sato K, Watanabe T, Konta T, Ueno Y, Kato T, Kayama T, Kubota I
  • Journal Title: Int J Med Sci. Volume: 10(1) Pages: 1-7
  • Peer Reviewed
• [Journal Article] Hyperhomocysteinaemia predicts the decline in pulmonary function in healthy male smokers (2013)
  • Author(s): Nunomiya K, Shibata Y, Abe S, Inoue S, Igarashi A, Yamauchi K, Aida Y, Kishi H, Sato M, Watanabe T, Konta T, Ueno Y, Kato T, Yamashita H, Kayama T, Kubota I
  • Journal Title: Eur Respir J. Volume: 42(1) Pages: 18-27
  • Peer Reviewed
• [Journal Article] A lower level of forced expiratory volume in 1 second is a risk factor for all-cause and cardiovascular mortality in a Japanese population: the Takahata Study.A lower level of forced expiratory volume in 1 second is a risk factor for all-cause and cardiovascular mortality in a Japanese population: the Takahata Study. (2013)
  • Author(s): Shibata Y et al.
  • Journal Title: PLOS ONE Volume: 8 Issue: 12 Pages: e83725-e83725
  • DOI: 10.1371/journal.pone.0083725
  • Peer Reviewed
• [Journal Article] Relationship between Plasma Fibrinogen Levels and Pulmonary Function in the Japanese Population: The Takahata Study. (2013)
  • Author(s): Shibata Y, et al.
  • Journal Title: Int J Med Sci Volume: 10 Issue: 11 Pages: 1530-1536
  • DOI: 10.7150/ijms.7256
  • Peer Reviewed
• [Journal Article] Elevated Serum Iron Is a Potent Biomarker for Spirometric Resistance to Cigarette Smoke among Japanese Males: The Takahata Study. (2013)
  • Author(s): Shibata Y et al.
  • Journal Title: PLOS ONE Volume: 8 Issue: 9 Pages: e74020-e74020
  • DOI: 10.1371/journal.pone.0074020
  • Peer Reviewed
• [Journal Article] Reduced Number and Morphofunctional Change of Alveolar Macrophages in MafB Gene-Targeted Mice. (2013)
  • Author(s): Sato-Nishiwaki M et al.
  • Journal Title: PLOS ONE Volume: 8 Issue: 9 Pages: e73963-e73963
  • DOI: 10.1371/journal.pone.0073963
  • Peer Reviewed
• [Journal Article] 5. Influence of corticosteroid therapy on the serum antibody response to influenza vaccine in elderly patients with chronic pulmonary diseases (2013)
  • Author(s): Sumito Inoue, Yoko Shibata, Noriaki Takabatake, Akira Igarashi, Shuichi Abe, Isao Kubota
  • Journal Title: EXCLI Journal Volume: 12 Pages: 760-765
  • Peer Reviewed
• [Journal Article] Retrospective analysis of the relationship between decline in FEV1 and abdominal circumference in male smokers: The Takahata Study (2013)
  • Author(s): Sato M, et al.
  • Journal Title: Int J Med Sci Volume: 10 Issue: 1 Pages: 1-7
  • DOI: 10.7150/ijms.5003
  • Peer Reviewed
• [Journal Article] Relationships between Values of Antibodies to Several Connective Tissue Disease Autoantigens and Pulmonary Function in a Japanese General Population: The Takahata Study. (2013)
  • Author(s): Nakano H et al.
  • Journal Title: PLOS ONE Volume: 8 Issue: 12 Pages: e81678-e81678
  • DOI: 10.1371/journal.pone.0081678
  • Peer Reviewed
• [Journal Article] Oxidized Phospholipid, 1-Palmitoyl- 2-(9'-Oxo-Nonanoyl)-Glycerophosphoc holine (PON-GPC), Produced in the Lung Due to Cigarette Smoking, Impairs Immune Function in Macrophages (2012)
  • Author(s): Kimura T, Shibata Y, Yamauchi K, Igarashi A, Inoue S, Abe S, Fujita K, Uosaki Y, Kubota I
  • Journal Title: Lung. Volume: 190(2) Pages: 169-182
  • Peer Reviewed
• [Journal Article] Hyperhomocysteinaemia predicts the decline in pulmonary function in healthy male smokers (2012)
  • Author(s): Nunomiya K, Shibata Y, Abe S, Inoue S, Igarashi A, Yamauchi K, Aida Y, Kishi H, Sato M, Watanabe T, Konta T, Ueno Y, Kato T, Yamashita H, Kayama T, Kubota I
  • Journal Title: Eur Respir J Volume: Nov Issue: 1 Pages: 18-27
  • DOI: 10.1183/09031936.00066212
  • Peer Reviewed
• [Journal Article] Oxidized phospholipid, 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC), produced in the lung due to cigarette smoking, impairs immune function in macrophages. (2012)
  • Author(s): Kimura T.
  • Journal Title: Lung Volume: 190 Issue: 2 Pages: 169-182
  • DOI: 10.1007/s00408-011-9331-2
  • Peer Reviewed
• [Journal Article] Impact of cigarette smoking on maximal expiratory flows in a general population : the Takahata study (2011)
  • Author(s): Nemoto T, Shibata Y, Osaka D, Abe S, Inoue S, Tokairin Y, Igarashi A, Yamauchi K, Kimura T, Kishi H, Nishiwaki M, Aida Y, Nunomiya K, Sato M, Watanabe T, Konta T, Kawata S, Kato T, Kayama T, Kubota I
  • Journal Title: Intern Med. Volume: 50(21) Pages: 2547-2555
  • NAID: 130001288610
  • Peer Reviewed
• [Journal Article] Impairment of Pulmonary Function is an Independent Risk Factor for Atrial Fibrillation : The Takahata Study (2011)
  • Author(s): Shibata Y, Watanabe T, Osaka D, Abe S, Inoue S, Tokairin Y, Igarashi A, Yamauchi K, Kimura T, Kishi H, Aida Y, Nunomiya K, Nemoto T, Sato M, Konta T, Kawata S, Kato T, Kayama T, Kubota I
  • Journal Title: Int J Med Sci. Volume: 8(7) Pages: 514-522
  • Peer Reviewed
• [Journal Article] The Relationship between Serum Uric Acid and Spirometric Values in Participants in a Health Check : The Takahata Study (2011)
  • Author(s): Aida Y, Shibata Y, Osaka D, Abe S, Inoue S, Fukuzaki K, Tokairin Y, Igarashi A, Yamauchi K, Nemoto T, Nunomiya K, Kishi H, Sato M, Watanabe T, Konta T, Kawata S, Kato T, Kubota I
  • Journal Title: Int J Med Sci. Volume: 8(6) Pages: 470-478
  • Peer Reviewed
• [Journal Article] Impact of Cigarette Smoking on Maximal Expiratory Flows in a General Population: the Takahata Study (2011)
  • Author(s): Nemoto T, Shibata Y, Osaka D, Abe S, Inoue S, et. al
  • Journal Title: Internal Medicine Volume: 50 Issue: 21 Pages: 2547-2555
  • DOI: 10.2169/internalmedicine.50.5948
  • NAID: 130001288610
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Impact of cigarette smoking on maximal expiratory flow in a general population : the Takahata Study (2011)
  • Author(s): Nemoto T, et al
  • Journal Title: Intern Med Volume: 50 Issue: 7 Pages: 2547-2555
  • DOI: 10.7150/ijms.8.514
  • Peer Reviewed
• [Journal Article] The Relationship between Serum Uric Acid and Spirometric Values in Participants in a Health Check: The Takahata Study (2011)
  • Author(s): Aida Y, Shibata Y, Osaka D, Abe S, Inoue S, et. al
  • Journal Title: Int J Med Sci. Volume: 8 Issue: 6 Pages: 470-8
  • DOI: 10.7150/ijms.8.470
  • Peer Reviewed
• [Journal Article] Soluble Endothelial Selectin in Acute Lung Injury Complicated by Severe Pneumonia (2011)
  • Author(s): Osaka D, et al
  • Journal Title: Int J Med Sci. Volume: 8 Issue: 4 Pages: 302-308
  • DOI: 10.7150/ijms.8.302
  • Peer Reviewed
• [Journal Article] FEV6 and FEV1/FEV6 in Japanese Participants of the Community-Based Annual Health Check: The Takahata Study (2011)
  • Author(s): Kishi H, Shibata Y, Osaka D, Abe S, Inoue S, et. al
  • Journal Title: Internal Medicine Volume: 50 Issue: 2 Pages: 87-93
  • DOI: 10.2169/internalmedicine.50.4276
  • NAID: 130000413204
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Immunohistochemical staining for transcription factor MafB in alveolar macrophages is correlated with spirometric measures of airflow limitation in smokers. (2011)
  • Author(s): Sato M, Shibata Y, Kimura T, Yamauchi K, Abe S, Inoue S, et. al
  • Journal Title: Respirology Volume: 16 Issue: 1 Pages: 124-30
  • DOI: 10.1111/j.1440-1843.2010.01886.x
  • Peer Reviewed
• [Presentation] The difference in the expression of Ern1 and the formation of granulomas in SPC-CCL1 Tg mice (2014)
  • Author(s): Sato M, Shibata Y, Kishi H, Abe S, Igarashi A, Yamauchi K, Aida Y, Nakano H, Sato K, Kimura T, Nunomiya K, Nemoto T, Inoue S, Kubota I
  • Organizer: American Thoracic Society 2014 International Conference
  • Place of Presentation: San Diego USA, (San Diego Convention Center)
• [Presentation] Lung-Specific CCL1 Overexpression Decreases Alveolar Macrophages In Murine BAL (2012)
  • Author(s): Kishi H, Igarashi A, Abe S, Yamauchi K, Sato M, Nemoto T, Nunomiya K, Aida Y, Inoue S, Kubota I, Shibata Y
  • Organizer: American Thoracic Society 2012 International Conference
  • Place of Presentation: San Francisco USA, (Moscone Convention Center)
• [Presentation] 肺特異的CCL1高発現マウスにおける生体内細胞分画の検討 (2012)
  • Author(s): 岸宏幸,阿部修一,柴田陽光,五十嵐朗,山内啓子,佐藤正道,根本貴子,布宮慶子,會田康子,井上純人,久保田功
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸(神戸コンベンションセンター)
• [Presentation] 喫煙一般住民において血清ホモシステイン(Hcy)高値は一秒量値の急速低下を予測する (2012)
  • Author(s): 布宮慶子，柴田陽光，阿部修一，井上純人，岸 宏幸，会田康子，山内啓子，根本貴子，佐藤正道，久保田功
  • Organizer: 第52回日本呼吸器学会総会
  • Place of Presentation: 神戸ｺﾝﾍﾞﾝｼｮﾝｾﾝﾀｰ (兵庫県)
• [Presentation] Dominant negative（DN）MafBトランスジェニックマウスを用いた急性肺障害モデルの検討 (2012)
  • Author(s): 會田康子，西脇道子，阿部修一，岸 宏幸，布宮慶子，山内啓子，井上純人，柴田陽光，久保田功
  • Organizer: 第52回日本呼吸器学会総会
  • Place of Presentation: 神戸ｺﾝﾍﾞﾝｼｮﾝｾﾝﾀｰ (兵庫県)
• [Presentation] 肺特異的CCL1高発現マウスにおける生体内細胞分画の検討 (2012)
  • Author(s): 岸 宏幸，阿部修一，柴田陽光，五十嵐朗，山内啓子，佐藤正道，根本貴子，布宮慶子，會田康子，井上純人，久保田功
  • Organizer: 第52回日本呼吸器学会総会
  • Place of Presentation: 神戸ｺﾝﾍﾞﾝｼｮﾝｾﾝﾀｰ (兵庫県)
• [Presentation] 肺癌患者における血清LYVE-1濃度の検討 (2012)
  • Author(s): 布宮慶子，柴田陽光，阿部修一，井上純人，岸 宏幸，会田康子，山内啓子，根本貴子，佐藤正道，久保田功
  • Organizer: 第52回日本呼吸器学会総会
  • Place of Presentation: 神戸ｺﾝﾍﾞﾝｼｮﾝｾﾝﾀｰ (兵庫県)
• [Presentation] 肺特異的CCLI発現マウスを用いた肺免疫機能の検討 (2011)
  • Author(s): 岸宏幸、井上純人 他
  • Organizer: 第51回日本呼吸器学会学術講演会
  • Place of Presentation: 東京 東京国際フォーラム
• [Presentation] Ccl1 is independent of inflammatory responses in LPS-stimulated lung injury in mice (2011)
  • Author(s): Kishi H, Inoue S. et. al
  • Organizer: American Thoracic Society 2011 International Conference
  • Place of Presentation: Ａｍｅｒｉｃａ Denver