期刊
FEBS JOURNAL
卷 281, 期 11, 页码 2543-2557出版社
WILEY-BLACKWELL
DOI: 10.1111/febs.12801
关键词
glycyrrhizin; lipid raft; mastitis; nuclear factor-B; Toll-like receptor4
资金
- National Natural Science Foundation of China [30972225, 30771596]
- Research Fund for the Doctoral Program of Higher Education of China [2011006-1130010]
Glycyrrhizin, a triterpene glycoside isolated from licorice root, is known to have anti-inflammatory activities. However, the effect of glycyrrhizin on mastitis has not been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of action of glycyrrhizin on lipopolysaccharide (LPS)-induced mastitis in mouse. An LPS-induced mouse mastitis model was used to confirm the anti-inflammatory activity of glycyrrhizin invivo. Primary mouse mammary epithelial cells were used to investigate the molecular mechanism and targets of glycyrrhizin. Invivo, glycyrrhizin significantly attenuated the mammary gland histopathological changes, myeloperoxidase activity and infiltration of neutrophilic granulocytes and downregulated the expression of tumor necrosis factor-, interleukin (IL)-1 and IL-6 caused by LPS. Invitro, glycyrrhizin dose-dependently inhibited the LPS-induced expression of tumor necrosis factor-, IL-6, and RANTES. Western blot analysis showed that glycyrrhizin suppressed LPS-induced nuclear factor-B and interferon regulatory factor3 activation. However, glycyrrhizin did not inhibit nuclear factor-B and interferon regulatory factor3 activation induced by MyD88-dependent (MyD88, IKK) or TRIF-dependent (TRIF, TBK1) downstream signaling components. Moreover, glycyrrhizin did not act though affecting the function of CD14 or expression of Toll-like receptor4. Finally, we showed that glycyrrhizin decreased the levels of cholesterol of lipid rafts and inhibited the translocation of Toll-like receptor4 to lipid rafts. Moreover, glycyrrhizin activated ATP-binding cassette transporterA1, which could induce cholesterol efflux from lipid rafts. In conclusion, we find that the anti-inflammatory effects of glycyrrhizin may be attributable to its ability to activate ATP-binding cassette transporterA1. Glycyrrhizin might be a useful therapeutic reagent for the treatment of mastitis and other inflammatory diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据