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Pharmacological preconditioning of lung with monophosphoryl lipid A: A role of MyD88-independent signaling pathway.

Research Project

Project/Area Number 24592087
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Thoracic surgery
Research InstitutionMie University

Principal Investigator

SHIMAMOTO AKIRA  三重大学, 医学部附属病院, 講師 (90324524)

Co-Investigator(Renkei-kenkyūsha) SHIMPO HIDETO  三重大学, 医学系研究科, 教授 (70179076)
TAKAO MOTOSHI  三重大学, 医学部附属病院, 准教授 (30263007)
TOMITA MASAYUKI  三重大学, 医学部附属病院, 臨床工学技士 (90774860)
MATSUO ERI  三重大学, 医学系研究科, 特定事業技術補佐員 (40751665)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords外科 / 移植・再生医療 / シグナル伝達
Outline of Final Research Achievements

In the present study, we evaluate the effect of monophosphoryl lipid A (MPL), an agonist of Toll-like receptor 4 (TLR4), on lung ischemia-reperfusion injury (LIRI), especially whether MPL affect pharmacological preconditioning (PPC) through a MyD88-independent signaling to protect against LIRI. C57BL/6 mice received MPL prior to 60 minutes of ischemia of their left lungs, followed by 180 minutes of reperfusion. Response to injury was quantified by tissue MPO activity, vascular permeability, and BAL expression. Lung homogenates were also analyzed for activation of MyD88, TRIF, and NF-κB. Pretreatment with MPL resulted in the development of a significant smaller LIRI. Instead of MyD88 activation, a strong activation of TRIF, leads to NF-κB activation in MyD88-independent signaling, is showing before LIRI same as ischemic preconditioning. We conclude that an activation of TRIF, which are associate proteins of TLR4, would regulate a role of NF-κB to preserve lung function.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (6 results)

All 2016 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Role of Heat Shock Proteins in Pharmacological Preconditioning for Lung Ischemia Reperfusion Injury2016

    • Author(s)
      A. Shimamoto, M. Takao, H. Shimpo
    • Journal Title

      The Journal of Heart and Lung Transplantation

      Volume: 35 Issue: 4 Pages: S185-S185

    • DOI

      10.1016/j.healun.2016.01.515

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Role of heat shock proteins in pharmacological preconditioning for lung ischemia reperfusion injury.2016

    • Author(s)
      Akira Shimamoto
    • Organizer
      The 36th Annual Meeting and Scientific Sessions of the ISHLT
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2016-04-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肺虚血再灌流障害におけるTLR4の働きに関する研究ー薬剤によるpreconditioning現象の確立に向けてー

    • Author(s)
      島本 亮
    • Organizer
      第113回日本外科学会学術集会
    • Place of Presentation
      福岡市
    • Related Report
      2013 Research-status Report
  • [Presentation] Pharmacological preconditioning of lung with monophosphoryl lipid A: A role of MyD88-independent signaling pathway.

    • Author(s)
      Akira Shimamoto
    • Organizer
      The 32nd Annual Meeting and Scientific Sessions of the ISHLT
    • Place of Presentation
      Prague, Czech Republic
    • Related Report
      2012 Research-status Report
  • [Presentation] HSP-70 is required for late-phase protection induced by pharmacological preconditioning of lung with monophosphoryl lipid A through MyD88-independent signaling pathway.

    • Author(s)
      島本 亮
    • Organizer
      第65回日本胸部外科学会定期学術集会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report
  • [Presentation] 肺虚血再灌流障害におけるTLR4の働きに関する研究ー薬剤によるpreconditioning現象の確立にむけて

    • Author(s)
      島本 亮
    • Organizer
      第113 回日本外科学会定期学術集会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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