Journal Article

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

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

2017

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Animals / Biomedical and Life Sciences / Biomedicine / 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 / Immunology / Internal Medicine / Macrophages - metabolism / Membrane Glycoproteins - drug effects / Membrane Glycoproteins - metabolism / Mice / Mice, Inbred C57BL / Myeloid Cells - metabolism / NF-kappa B - metabolism / Original Article / Pathology / Pharmacology/Toxicology / Phenylurea Compounds - pharmacology / Piperidines - pharmacology / Pneumonia - drug therapy / Receptors, Immunologic - drug effects / Receptors, Immunologic - metabolism / Rheumatology / Solubility / Triggering Receptor Expressed on Myeloid Cells-1