Effects of trichostatin A on the expressions of inflammatory cytokines and toll-like receptor 4 and the acetylation of nuclear factor-κB induced by lipopolysaccharide in macrophage.
- Author:
Xiao-Lan HU
1
;
Xiao ZHANG
;
Qian LI
;
Shui-Feng QIU
;
Ru-Huan MEI
Author Information
1. Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China. huxiaolan1998@yahoo.com.cn
- Publication Type:Journal Article
- MeSH:
Acetylation;
Animals;
Cell Line;
Hydroxamic Acids;
pharmacology;
Inflammation;
metabolism;
Interleukin-1beta;
metabolism;
Interleukin-6;
metabolism;
Lipopolysaccharides;
Macrophages;
drug effects;
metabolism;
Mice;
Signal Transduction;
Toll-Like Receptor 4;
metabolism;
Transcription Factor RelA;
metabolism;
Tumor Necrosis Factor-alpha;
metabolism;
Up-Regulation
- From:
Acta Physiologica Sinica
2012;64(6):651-656
- CountryChina
- Language:Chinese
-
Abstract:
The present study aims to explore the possible mechanisms that trichostatin A (TSA), a histone deacetylases inhibitor (HDACi), affects the inflammatory signaling pathways of lipopolysaccharide/toll-like receptor 4/nuclear factor-κB (LPS/TLR4/NF-κB). Murine macrophage cell line RAW264.7 cells were employed. MTT assay was used to assess cell viability. The contents of TNF-α, IL-1β and IL-6 in culture supernatant were assayed by enzyme-linked immunosorbent assay (ELISA). TLR4 expression and NF-κB/p65 (Lys310) acetylation were examined by Western blotting. DNA binding activity of NF-κB/p65 was detected by using TransAM(TM) NF-κB/p65 activity assay kit. The results showed that, compared with control group, which was treated by DMSO, the cells treated with TSA (20, 40, 80 ng/mL) showed decreased percentages of cell survival (P < 0.05). The contents of TNF-α, IL-1β and IL-6 in culture supernatant were all increased by LPS (100 ng/mL), whereas reduced by 40 ng/mL TSA pretreatment (P < 0.05). TSA pretreatment inhibited LPS-induced up-regulation of TLR4 protein expression. Acetylation of NF-κB/p65(Lys310), which was already increased by LPS, was further enhanced by TSA (P < 0.05). On the contrary, LPS-increased DNA binding activity of NF-κB/p65 was decreased by pretreatment with TSA (P < 0.05). The results suggest that TSA-induced anti-inflammation may be attributed to decreases in the expression of TLR4 and DNA binding activity of NF-κB/p65.
