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[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.] [Article in Chinese]

HU Xiao-Lan^*, ZHANG Xiao, Li Qian, QIU Shui-Feng, MEI Ru-Huan

Department of Physiology, Zhejiang University School of Medicine, 588 Yuhangtang Road, Hangzhou 310058, China

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.

Key words: histone deacetylases inhibitor; lipopolysaccharide; Toll-like receptor 4; nuclear factor-κB; inflammatory factor

Received: 2012-04-26　　Accepted: 2012-06-19

Corresponding author: 胡晓兰　　E-mail: huxiaolan1998@yahoo.com.cn

Citing This Article：

HU Xiao-Lan, ZHANG Xiao, Li Qian, QIU Shui-Feng, MEI Ru-Huan. [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.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (6): 651-656 (in Chinese with English abstract).