| Project/Area Number |
23591121
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOICHIRO Matsumoto 九州大学, 九州大学病院, 講師 (60325462)
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| 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
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥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)
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| 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 |
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| 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.
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