期刊
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
卷 90, 期 3, 页码 -出版社
WILEY
DOI: 10.1111/sji.12791
关键词
epoxyeicosatrienoic acids; free fatty acid; macrophage; non-alcoholic fatty liver disease; soluble epoxide hydrolase
类别
资金
- National Natural Science Foundation of China [81500452] Funding Source: Medline
- Innovation Team Development Plan of the Ministry of Education [IRT_14R20] Funding Source: Medline
- National Science and Technology Major Project [2018ZX10302206-001-010] Funding Source: Medline
The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases and have recently been found to have an anti-inflammatory activity. However, the role of EETs in non-alcoholic steatohepatitis has not been fully understood. In this study, we investigated the protective role of EETs in methionine-choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH) in mice and the potential mechanisms. We used 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea(TPPU), a soluble epoxide hydrolase inhibitor, to increase the endogenous EET level in mice. Upon TPPU treatment, the liver steatosis and inflammatory damage were significantly ameliorated in mice with steatohepatitis, paralleled by the downregulation of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6) as well as chemokines (CXCL1, MCP-1). Compared with untreated NASH mice, mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and inflammation relevant adhesion molecules (ICAM-1, VCAM-1) were downregulated, whereas mRNA level of peroxisome proliferator-activated receptor alpha(PPAR-alpha) was elevated in TPPU-treated mice. In vitro, 11,12-EET treatment remarkably attenuated free fatty acid (FFA)-induced inflammation in HepG2 and THP-1 cells. Further, 11,12-EET inhibited the activation of NF-kappa B signalling pathway in macrophages from mice with steatohepatitis. Collectively, these results suggest that EETs play a protective role and alleviate the MCD diet-induced steatohepatitis in mice mainly by downregulating activation of NF-kappa B pathway in macrophages.
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