Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2
10.16438/j.0513-4870.2022-1406
- VernacularTitle:曲古抑菌素C通过上调Krüppel样转录因子2抑制TNFα诱导的内皮细胞炎症
- Author:
Li-juan LEI
;
Ming-hua CHEN
;
Ying-hong LI
;
Xin-hai JIANG
;
Wei-zhi WANG
;
Li-ping ZHAO
;
Chen-yin WANG
;
Yu-chuan CHEN
;
Yu-yan ZHANG
;
Ye-xiang WU
;
Shun-wang LI
;
Jiang-xue HAN
;
Yi-ning LI
;
Ren SHENG
;
Yu-hao ZHANG
;
Jing ZHANG
;
Li-yan YU
;
Shu-yi SI
;
Yan-ni XU
- Publication Type:Research Article
- Keywords:
trichostatin C;
Krüppel-like factor 2;
endothelial inflammation;
atherosclerosis;
vascular cell adhesion molecule-1;
histone deacetylase
- From:
Acta Pharmaceutica Sinica
2023;57(8):2375-2383
- CountryChina
- Language:Chinese
-
Abstract:
Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.
