title: Soluble Epoxide Hydrolase Inhibitor Suppresses the Expression of Triggering Receptor Expressed on Myeloid Cells-1 by Inhibiting NF-kB Activation in Murine Macrophage.
abstract: Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. TREM-1 amplifies the inflammatory response. Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 enzyme, have anti-inflammatory properties. However, the effects of EETs on TREM-1 expression under inflammatory stimulation remain unclear. Therefore, inhibition of soluble epoxide hydrolase (sEH) with a highly selective inhibitor [1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) 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 treatment-alleviated LPS-induced pulmonary inflammation. TPPU decreased TREM-1 expression, but not DAP12 or MyD88 expression. Murine peritoneal macrophages were challenged with LPS in vitro. We found that TPPU reduced LPS-induced TREM-1 expression in a dose-dependent manner, but not DAP12 or MyD88 expression. TPPU also decreased downstream signal from TREM-1, reducing pro-inflammatory cytokine TNF-α and IL-1β mRNA expression. Furthermore, TPPU treatment inhibited IkB degradation in vivo and in vitro. Our results indicate that the inhibition of sEH suppresses LPS-induced TREM-1 expression and inflammation via inhibiting NF-kB activation in murine macrophage.
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China.|Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, 56300, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, 56300, China.
authors.forename: Zhao-Qiong
authors.initials: ZQ
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China.
authors.forename: Jia-Xi
authors.initials: JX
authors.lastname: Duan
authors.affiliation: Department of Physiology, Hunan University of Medicine, Huaihua, Hunan, 410208, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Departments of Entomology and the UC Davis Cancer Center, University of California Davis, Davis, CA, 95616, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammcok
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China. guanchaxiang@csu.edu.cn.
authors.forename: Cha-Xiang
authors.initials: CX
authors.lastname: Guan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D015870:Gene Expression / Q000187:drug effects; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011014:Pneumonia / Q000188:drug therapy; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D012995:Solubility; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: C581572:1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea; D016207:Cytokines; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010671:Phenylurea Compounds; D010880:Piperidines; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D004851:Epoxide Hydrolases
keywords: epoxyeicosatrienoic acids; inflammation; macrophage; soluble epoxide hydrolase inhibitor; triggering receptor expressed on myeloid cells-1