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World J Gastroenterol. 2015 Jul 7;21(25):7764-76. doi: 10.3748/wjg.v21.i25.7764.

Overexpression of HMGB1 A-box reduced lipopolysaccharide-induced intestinal inflammation via HMGB1/TLR4 signaling in vitro.

Author information

1
Fu-Cai Wang, Jing-Xuan Pei, Dong-Sheng Liu, Hui-Fang Xiong, Xiao-Qun Liu, Yong Xie, Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Gastroenterology Institute of Jiangxi Province, Key Laboratory of Digestive Diseases of Jiangxi Province, Nanchang 330006, Jiangxi Province, China.

Abstract

AIM:

To investigate the inhibitory effects and mechanism of high mobility group box (HMGB)1 A-box in lipopolysaccharide (LPS)-induced intestinal inflammation.

METHODS:

Overexpression of HMGB1 A-box in human intestinal epithelial cell lines (SW480 cells) was achieved using the plasmid pEGFP-N1. HMGB1 A-box-overexpressing SW480 cells were stimulated with LPS and co-culturing with human monocyte-like cell lines (THP-1 cells) using a Transwell system, compared with another HMGB1 inhibitor ethyl pyruvate (EP). The mRNA and protein levels of HMGB1/toll-like receptor (TLR) 4 signaling pathways [including HMGB1, TLR4, myeloid differentiation factor88 (MYD88), Phosphorylated Nuclear Factor κB (pNF-κB) p65] in the stimulated cells were determined by real-time polymerase chain reaction and Western blotting. The levels of the proinflammatory mediators [including HMGB1, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α] in the supernatants of the stimulated cells were determined by ELISA.

RESULTS:

EP downregulated the mRNA and protein levels of HMGB1, inhibited the TLR4 signaling pathways (TLR4, MYD88 and pNF-κB p65) and reduced the secretion of proinflammatory mediators (HMGB1, IL-1β, IL-6 and TNF-α) in the SW480 and THP-1 cells activated by LPS but not in the unstimulated cells. Activated by LPS, the overexpression of HMGB1 A-box in the SW480 cells also inhibited the HMGB1/TLR4 signaling pathways and reduced the secretion of these proinflammatory mediators in the THP-1 cells but not in the transfected and unstimulated cells.

CONCLUSION:

HMGB1 A-box, not only EP, can reduce LPS-induced intestinal inflammation through inhibition of the HMGB1/TLR4 signaling pathways.

KEYWORDS:

Ethyl pyruvate; HMGB1 A-box; High mobility group box 1; Inflammatory bowel disease; Toll-like receptor 4

PMID:
26167076
PMCID:
PMC4491963
DOI:
10.3748/wjg.v21.i25.7764
[Indexed for MEDLINE]
Free PMC Article

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