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

被引：0

作者：

Fu-Cai Wang ^{[1
,2
]}

Jing-Xuan Pei ^{[1
]}

Jun Zhu ^{[3
]}

Nan-Jin Zhou ^{[4
]}

Dong-Sheng Liu ^{[1
]}

Hui-Fang Xiong ^{[1
]}

Xiao-Qun Liu ^{[1
]}

Dong-Jia Lin ^{[2
]}

Yong Xie ^{[1
]}

机构：

[1] Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Gastro-enterology Institute of Jiangxi Province, Key Laboratory of Digestive Diseases of Jiangxi Province

[2] Department of Immunology, Medical College of Nanchang University

[3] Department of Pathophysiology, Medical College of Nanchang University

[4] Institute of Immunology and Biological Therapy, Jiangxi Academy of Medical Sciences

来源：

World Journal of Gastroenterology | 2015年 / 25期

基金：

中国国家自然科学基金;

关键词：

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

D O I：

暂无

中图分类号：

R574 [肠疾病];

学科分类号：

1002 ; 100201 ;

摘要：

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 p EGFP-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 m RNA and protein levels of HMGB1/toll-like receptor(TLR) 4 signaling pathways [including HMGB1, TLR4, myeloid differentiation factor88(MYD88), Phosphorylated Nuclear Factor κB(p NF-κB) p65] in the stimulated cells were determined by realtime 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 m RNA and protein levels of HMGB1, inhibited the TLR4 signaling pathways(TLR4, MYD88 and p NF-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.

引用

页码：7764 / 7776

页数：13