Geraniin Inhibits LPS-Induced THP-1 Macrophages Switching to M1 Phenotype via SOCS1/NF-κB Pathway.
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 α (TNF-α) 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-κB-p65 and NF-κB-p65 expression without affecting the level of IκB-α. This suggested that geraniin inhibited NF-κB, 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-κB to the nucleus. Moreover, we found that geraniin up-regulated the expression of SOCS1, an upstream regulator of NF-κB activation that can directly bind to NF-κB-p65 and downregulate it, thus inhibiting NF-κB activation. In conclusion, geraniin inhibits LPS-induced THP-1 macrophages switching to M1 phenotype through SOCS1/NF-κB pathway.
Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.|Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China.
Xinxin
X
Liu
Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.|Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China.
Ji
J
Li
Heilongjiang Province Lumber Industry General Hospital, Harbin, 150040, China.
Xiaohong
X
Peng
Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.|Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China.
Bo
B
Lv
Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, China.
Peng
P
Wang
Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. David.Zhao@Vanderbilt.Edu.|Department of Cardiology, Vanderbilt University Medical Center, Nashville, 37232, USA. David.Zhao@Vanderbilt.Edu.
Xiaoming
X
Zhao
Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. dryu_hmu@163.com.|Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China. dryu_hmu@163.com.
Bo
B
Yu
D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics
D016207:Cytokines; D005960:Glucosides; D047348:Hydrolyzable Tannins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D051996:Transcription Factor RelA; C024603:Geraniin
NF-κB; SOCS1; geraniin; inflammation; macrophage polarization