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Publication Detail

Title: Soluble Epoxide Hydrolase Inhibitor Suppresses the Expression of Triggering Receptor Expressed on Myeloid Cells-1 by Inhibiting NF-kB Activation in Murine Macrophage.

Authors: Dong, Liang; Zhou, Yong; Zhu, Zhao-Qiong; Liu, Tian; Duan, Jia-Xi; Zhang, Jun; Li, Ping; Hammcok, Bruce D; Guan, Cha-Xiang

Published In Inflammation, (2017 Feb)

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.

PubMed ID: 27696333 Exiting the NIEHS site

MeSH Terms: Animals; Cells, Cultured; Cytokines/drug effects; Cytokines/metabolism; Epoxide Hydrolases/antagonists & inhibitors*; Gene Expression/drug effects; I-kappa B Proteins/drug effects; I-kappa B Proteins/metabolism; Macrophages/metabolism; Membrane Glycoproteins/drug effects; Membrane Glycoproteins/metabolism*; Mice; Mice, Inbred C57BL; Myeloid Cells/metabolism*; NF-kappa B/metabolism*; Phenylurea Compounds/pharmacology; Piperidines/pharmacology; Pneumonia/drug therapy; Receptors, Immunologic/drug effects; Receptors, Immunologic/metabolism*; Solubility; Triggering Receptor Expressed on Myeloid Cells-1

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