The crucial role of PLCepsilon in a mouse model of acute lung injury

• Project/Area Number: 26461188
• 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: Kobe University
• Principal Investigator: KOBAYASHI KAZUYUKI 神戸大学, 医学研究科, 講師 (50403275)
• Co-Investigator(Kenkyū-buntansha): 西村 善博 神戸大学, 医学部附属病院, 特命教授 (20291453) ; 永野 達也 神戸大学, 医学研究科, 特命助教 (80624684) ; 田村 大介 神戸大学, 医学部附属病院, 非常勤講師 (80646597)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: PLCε / ALI / PhospholipaseCepsilon / ARDS / 急性肺障害 / phospholipaseCε

Outline of Final Research Achievements

Phospholipase Cε (PLCε) is an effector of Ras and Rap small GTPases. The aim of this study is to examine whether PLCε is involved also in the pathogenesis of neutrophil-mediated airway inflammation. Acute lung injury (ALI) was experimentally induced by intratracheal administration of LPS in PLCε knock out (KO) mice. In contrast with PLCε wild type (WT) mice, the accumulation of inflammatory cells in the alveolar space were substantially reduced in PLC KO mice. Comparison of the cytokine mRNA levels of the total lungs by qRT-PCR of LPS-stimulated mice indicated that PLCε deficiency attenuated the LPS-induced expression of the CXC family chemokines. These results suggest that PLCε mediated induction of the CXC family chemokines by the structural cells plays an important role in neutrophil mediated airway inflammation and that PLCε could be a molecular target for the treatment of patients with ARDS.

Research Products

• [Presentation] A mouse model of acute lung injury implicates phospholipase Cε in neutrophilic inflammation through CXC chemokine production (2016)
  • Author(s): Kanoko Umezawa, Tatsuya Nagano, Hironori Edamatsu, Haruka Nshimura, Daisuke Tamura, Kazuyuki Kobayashi, Tohru Kataoka, Yoshihiro Nishimura
  • Organizer: ERS International Congress 2016
  • Place of Presentation: London, UK
  • Year and Date: 2016-09-04
• [Presentation] 急性呼吸窮迫症候群におけるホスホリパーゼCεの役割 (2016)
  • Author(s): 梅澤佳乃子、永野達也、小林和幸、田村大介、西村春佳、西村善博
  • 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
  • Year and Date: 2016-04-09