DC-SIGN Expression in Intestinal Epithelial Cells Regulates Sepsis-Associated Acute Intestinal Injury Via Activating ERK1/2-NF-κB/P65 Signaling

被引:13
作者
Chen, Weiwei [1 ]
Ma, Li [1 ]
Li, Ranran [2 ]
Huang, Shunwei [1 ]
Xie, Rongli [3 ]
Chen, Ying [1 ]
Zhao, Bing [1 ]
Fei, Jian [3 ]
Qu, Hongping [2 ]
Chen, Hao [3 ]
Mao, Enqiang [1 ]
Chen, Er-zhen [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Emergency, Ruijin Er Rd 197, Shanghai 200025, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Crit Care Med, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Surg, Ruijin Er Rd 197, Shanghai 200025, Peoples R China
来源
SHOCK | 2019年 / 52卷 / 04期
基金
中国国家自然科学基金;
关键词
Acute intestinal injury; DC-SIGN; ERK1; 2; intestinal epithelial cells; NF-kappa B; sepsis; C-TYPE LECTINS; DENDRITIC CELLS; FAILURE; PATHOGENESIS; LIGATION; GUT;
D O I
10.1097/SHK.0000000000001277
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objective: The aim of the study was to investigate the role of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in intestinal epithelial cells (IECs) in regulating sepsis-induced acute intestinal injury and systemic inflammatory response. Methods: To induce sepsis condition, Male C57BL/6 mice were exposed to cecal ligation and puncture (CLP) in vivo, whereas a normal human IECs line (FHs74Int) was stimulated with lipopolysaccharide (LPS) in vitro. DC-SIGN siRNA pretreatment was used to knock down DC-SIGN expression both in vivo and in vitro. The expression of DC-SIGN was detected by western blot and immunohistochemistry. The expression of total and phosphorylation of ERK1/2 and NF-kappa B/p65 was examined by western blot. The levels of cytokines in serum and culture supernatant were measured by ELISA. The survival rate and organ injures of septic mice were also assessed. Results: In vivo, DC-SIGN expression in mouse IECs was time-dependently upregulated by CLP. CLP-induced phosphorylation of ERK1/2 and NF-kappa B/p65 was effectively inhibited by DC-SIGN siRNA pretreatment, leading to the decrease of systemic inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-10, and IFN-gamma), which alleviated multiple organ injuries and increased the survival rate of septic mice. In vitro, DC-SIGN expression in FHs74Int was significantly upregulated by LPS stimulation in a time- and dose-dependent manner. DC-SIGN knockdown abolished LPS-induced ERK1/2 and NF-kappa B/p65 phosphorylation, resulting in the decrease of cytokines release by FHs74Int. Conclusions: Sepsis-induced DC-SIGN expression in IECs plays a significant role in regulating acute intestinal injury and systemic inflammatory response. The inhibition of DC-SIGN exhibited protective effects on sepsis-associated organ injury and systemic inflammation.
引用
收藏
页码:434 / 442
页数:9
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