Obeticholic acid alleviate lipopolysaccharide-induced acute lung injury via its anti-inflammatory effects in mice

被引:38
作者
Fei, Jun [1 ,2 ]
Fu, Lin [3 ,4 ]
Hu, Biao [1 ]
Chen, Yuan-Hua [4 ,5 ]
Zhao, Hui [1 ]
Xu, De-Xiang [3 ,4 ]
Li, Jia-Bin [2 ,6 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Infect Dis, Jixi Rd 218, Hefei 230032, Anhui, Peoples R China
[2] Anhui Med Univ, Affiliated Hosp 2, Hefei 230032, Anhui, Peoples R China
[3] Anhui Med Univ, Dept Toxicol, 81 Meishan Rd, Hefei 230032, Anhui, Peoples R China
[4] Anhui Prov Key Lab Populat Hlth & Aristogen, Hefei 230032, Anhui, Peoples R China
[5] Anhui Med Univ, Dept Histol & Embryol, Hefei 230032, Anhui, Peoples R China
[6] Anhui Ctr Surveillance Bacterial Resistance, Hefei 230032, Anhui, Peoples R China
基金
中国国家自然科学基金;
关键词
Obeticholic acid; Inflammation; Acute lung injury; Famesoid X receptor; NP-kappa B; MAPKs; GROWTH RESTRICTION; SIGNALING PATHWAYS; LIVER-INJURY; RAT MODEL; RECEPTOR; INFLAMMATION; MACROPHAGE; RESPONSES; PROTECTS; OUTCOMES;
D O I
10.1016/j.intimp.2018.11.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Acute lung injury (ALI) is a common disease that may result in acute respiratory failure and death. However, there are still no effective treatments for ALI. Several studies have shown that farnesoid X receptor (FXR) has an anti-inflammatory effect. We investigated the effects of obeticholic acid (OCA), an agonist of FXR, on Lipopolysaccharide (LPS)-induced ALI in mice. Sixty male mice were randomly divided into six groups, and orally administered with or without OCA once daily for 3 consecutive days before LPS (1.0 mg/kg). Animals were sacrificed at 0 h, 2 h or 6 h after LPS. As expected, OCA enhanced pulmonary FXR activity. OCA prevented LPS-induced ALI. Additional experiment showed that OCA alleviated LPS-induced up-regulation of pulmonary pro-inflammatory and chemokine genes. Moreover, OCA also repressed LPS-induced the release of TNF-alpha and KC in serum and bronchoalveolar lavage fluid. In contrast, OCA further up-regulated LPS-induced the expression of Il-10, an anti-inflammatory cytokine. Further study showed that OCA inhibited LPS-evoked NF-kappa B signaling in the lungs. OCA attenuated LPS-induced ERK1/2, JNK, p38 and Akt phosphorylation in the lungs. Overall, these results suggest that OCA prevent LPS-induced ALI may be through enhancing pulmonary FXR activity and then blockading several inflammatory signaling pathways.
引用
收藏
页码:177 / 184
页数:8
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