Pharmacological preconditioning of lung with monophosphoryl lipid A: A role of MyD88-independent signaling pathway.
| Project/Area Number |
24592087
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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 |
Thoracic surgery
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| Research Institution | Mie University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| 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)
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| Keywords | 外科 / 移植・再生医療 / シグナル伝達 |
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| 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.
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Report
(5 results)
Research Products
(6 results)
