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Title of Journal: Inflammation

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Abbravation: Inflammation

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Springer US

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DOI

10.1002/hyp.1247

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1573-2576

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Soluble Epoxide Hydrolase Inhibitor Suppresses the

Authors: Liang Dong Yong Zhou ZhaoQiong Zhu Tian Liu JiaXi Duan Jun Zhang Ping Li Bruce D Hammcok ChaXiang Guan
Publish Date: 2016/10/01
Volume: 40, Issue: 1, Pages: 13-20
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Abstract

Triggering receptors expressed on myeloid cell1 TREM1 is a superimmunoglobulin receptor expressed on myeloid cells TREM1 amplifies the inflammatory response Epoxyeicosatrienoic acids EETs the metabolites of arachidonic acid derived from the cytochrome P450 enzyme have antiinflammatory properties However the effects of EETs on TREM1 expression under inflammatory stimulation remain unclear Therefore inhibition of soluble epoxide hydrolase sEH with a highly selective inhibitor 1trifluoromethoxyphenyl31propionylpiperidin4yl urea TPPU was used to stabilize EETs LPS was intratracheally injected into mice to induce pulmonary inflammation after TPPU treatment for 3 h Histological examination showed TPPU treatmentalleviated LPSinduced pulmonary inflammation TPPU decreased TREM1 expression but not DAP12 or MyD88 expression Murine peritoneal macrophages were challenged with LPS in vitro We found that TPPU reduced LPSinduced TREM1 expression in a dosedependent manner but not DAP12 or MyD88 expression TPPU also decreased downstream signal from TREM1 reducing proinflammatory cytokine TNFα and IL1β mRNA expression Furthermore TPPU treatment inhibited IkB degradation in vivo and in vitro Our results indicate that the inhibition of sEH suppresses LPSinduced TREM1 expression and inflammation via inhibiting NFkB activation in murine macrophageThis work was supported by the National Natural Science Foundation of China No 81500065 81670014 the Specialized Research Fund for the Doctoral Program of Higher Education of China 20130162110052 High School Innovation Fund of Hunan province 15K140 and the OpenEnd Fund for the Valuable and Precision Instruments of Central South University CSUCZ201632Conceived and designed the experiments CXG LD YZ Performed the experiments LD YZ TL PL Analyzed the data LD JXD JZ YZ Contributed reagents/materials/analysis tools YZ BDH CXG Wrote the paper LD YZ CXG Critically reviewed the manuscript BDH CXG


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