期刊
INFLAMMATION
卷 39, 期 4, 页码 1421-1433出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-016-0374-7
关键词
geraniin; inflammation; macrophage polarization; NF-kappa B; SOCS1
资金
- National Natural Science Foundation of China [81330033]
- National Natural Science Funds for Young Scholar [81400296]
- China Postdoctoral Science Foundation [2015M581483]
- Heilongjiang Postdoctoral Fund [LBH-Z15161]
- Key Laboratory of Myocardial Ischemia (Harbin Medical University), Ministry of Education [KF201507, KF201411]
M1 macrophage polarization is proved to promote inflammation in atherosclerosis process. In this study, we evaluated the inhibitory effect of geraniin, a bioactive polyphenolic compound, on the LPS-induced switch of THP-1 macrophages to M1 phenotype, and we propose a molecular basis for its action. Flow cytometry analysis indicated that geraniin significantly inhibited LPS-induced M1 macrophage polarization. Geraniin downregulated the protein and the mRNA level of typical cytokines of M1 macrophage, including tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), indicating that geraniin can suppress typical mediators of M1 macrophage at the transcriptional level. Moreover, geraniin inhibited LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) production, as well as inducible nitric oxide synthase (iNOS) activity, in THP-1 macrophages. Furthermore, western blot analysis indicated that geraniin decreased both LPS-induced phosphorylation of NF-kappa B-p65 and NF-kappa B-p65 expression without affecting the level of I kappa B-alpha. This suggested that geraniin inhibited NF-kappa B, a transcription factor pivotal in the LPS-induced expression of pro-inflammatory genes and an important player in M1 macrophage polarization. Moreover, an electrophoretic mobility shift assay (EMSA) demonstrated that geraniin blocked the LPS-induced translocation of NF-kappa B to the nucleus. Moreover, we found that geraniin up-regulated the expression of SOCS1, an upstream regulator of NF-kappa B activation that can directly bind to NF-kappa B-p65 and downregulate it, thus inhibiting NF-kappa B activation. In conclusion, geraniin inhibits LPS-induced THP-1 macrophages switching to M1 phenotype through SOCS1/NF-kappa B pathway.
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