The roles of SOCS in obstructive pulmonary diseases

• Project/Area Number: 23591121
• 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: Kyushu University
• Principal Investigator: SATORU FUKUYAMA 九州大学, 大学病院, 助教 (50380530)
• Co-Investigator(Kenkyū-buntansha): KOICHIRO Matsumoto 九州大学, 九州大学病院, 講師 (60325462)
• Co-Investigator(Renkei-kenkyūsha): HIRAI Hiroko 九州大学, 大学院医学研究院呼吸器内科学, 大学院生 ; YUKARI Tajiri 九州大学, 大学院医学研究院呼吸器内科学, 大学院生 ; NAOTAKA Noda 九州大学, 大学院医学研究院呼吸器内科学, 大学院生 ; YUKO Matsunaga 九州大学, 大学院医学研究院呼吸器内科学, 大学院生
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: SOCS / 喘息 / COPD / エフェロサイトーシス / 気管支喘息 / 慢性閉塞性肺疾患

Research Abstract

Allergic airway inflammation and airway responsiveness to inhaled Ach were attenuated in airway epithelium specific SOCS3 knockout (SOCS3/CC10Cre) mice than in wild type mice.
Apoptotic cell phagocytosis by alveolar macrophage (AM) is called efferocytosis. Pre-treatment of alveolar macrophage (AMs) with cigarette smoke extract (CSE) or trichostatin A (TSA), an HDAC inhibitor, suppressed efferocytosis and CSE reduced HDAC activity. TSA inhibited the activity of Rac, a key mediator of efferocytosis. These TSA-induced impairments were restored by treatment of AMs with aminophylline, a potent activator of HDAC. TSA profoundly down-regulated the expression of CD9 on AMs. The expression of CD9 was partly down-regulated by the Rac inhibitor. Pretreatment with an anti-CD9 mAb or CD9 siRNA inhibited efferocytosis, which was attributable to the reduced binding of AMs to apoptotic cells. These results suggest that smoking impairs efferocytosis via inhibition of HDAC/Rac/CD9 pathways.

Research Products

• [Journal Article] Cigarette smoke impairs phagocytosis of apoptotic neutrophils by alveolar macrophages via inhibition of the histone deacetylase/Rac/CD9 pathways (2013)
  • Author(s): Noda N, Matsumoto K, Fukuyama S, Asai Y, Kitajima H, Seki N, Matsunaga Y, Kan-O K, Moriwaki A, Morimoto K, Inoue H, Nakanishi Y
  • Journal Title: Int Immunol Volume: 25(11) Pages: 643-50
  • Peer Reviewed
• [Journal Article] Cigarette smoke impairs phagocytosis of apoptotic neutrophils by alveolar macrophages via inhibition of the histone deacetylase/Rac/CD9 pathways. (2013)
  • Author(s): Noda N, Matsumoto K, Fukuyama S, Asai Y, Kitajima H, Seki N, Matsunaga Y, Kan-O K, Moriwaki A, Morimoto K, Inoue H, Nakanishi Y.
  • Journal Title: International Immunology Volume: 25 Pages: 643-650
  • Peer Reviewed
• [Journal Article] A zinc chelator TPEN attenuates airway hyperresponsiveness and airway inflammation in mice in vivo (2011)
  • Author(s): Fukuyama S, Matsunaga Y, Zhanghui W, Noda N, Asai Y, Moriwaki A, Matsumoto T, Nakano T, Matsumoto K, Nakanishi Y, Inoue H
  • Journal Title: Allergol Int Volume: 60(3) Pages: 259-66
  • NAID: 130004723036
  • Peer Reviewed
• [Presentation] 慢性抗原曝露と気道リモデリング (2012)
  • Author(s): 福山聡
  • Organizer: 第24回日本アレルギー学会春季臨床大会
  • Place of Presentation: 大阪
  • Year and Date: 2012-05-12
• [Presentation] JAK阻害薬#69の好酸球性気道炎症への影響 (2012)
  • Author(s): 北島裕子、福山聡、松元幸一郎、井上博雅、中西洋一
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪市
• [Presentation] 亜鉛キレート剤TPENのマウス喘息モデルにおける気道過敏性と好酸球性気道炎症への抑制効果 (2011)
  • Author(s): 福山聡、松永悠子、浅井友香里、神尾敬子、北島裕子、濵野紗朱、松元幸一郎、井上博雅、中西洋一
  • Organizer: 第51回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2011-04-22
• [Remarks] 九州大学大学院医学研究院胸部疾患研究施設
  • URL: http://www.kokyu.med.kyushu-u.ac.jp