Inhibitions of NF-κB and TNF-α Result in Differential Effects in Rats with Acute on Chronic Liver Failure Induced by d-Gal and LPS

被引：73

作者：

Yang, Fan ^{[1
]}

Li, Xun ^{[1
]}

Wang, Li-kun ^{[1
]}

Wang, Lu-wen ^{[1
]}

Han, Xiao-qun ^{[1
]}

Zhang, Hong ^{[2
]}

Gong, Zuo-jiong ^{[1
]}

机构：

[1] Wuhan Univ, Renmin Hosp, Dept Infect Dis, Wuhan 430060, Hubei Province, Peoples R China

[2] Wuhan Univ, Renmin Hosp, Dept Pharmaceut, Wuhan 430060, Hubei Province, Peoples R China

来源：

INFLAMMATION | 2014年 / 37卷 / 03期

基金：

中国国家自然科学基金;

关键词：

acute-on-chronic liver failure; inflammation; NF-kappa B; TNF-alpha; pyrrolidine dithiocarbamate; MOBILITY GROUP BOX-1; CHROMATIN PROTEIN HMGB1; PYRROLIDINE DITHIOCARBAMATE; RHEUMATOID-ARTHRITIS; LATE MEDIATOR; INFLAMMATION; PATHWAY; INJURY; CHROMOSOMAL-PROTEIN-1; ENDOTOXEMIA;

D O I：

10.1007/s10753-013-9805-x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

In this study, we induced an acute-on-chronic liver failure (ACLF) model by human serum albumin (HSA), d-galactosamine (d-Gal) and lipopolysaccharide (LPS) in rats. Anti-TNF-alpha polyclonal antibody (as TNF-alpha inhibitor) and pyrrolidine dithiocarbamate (PDTC, a NF-kappa B inhibitor) were used to treat the liver failure animals, respectively. The results showed that TNF-alpha inhibition was beneficial, but NF-kappa B inhibition failed to protect the rats in ACLF. However, HMGB1 levels, cytokine production and activation of TLR4-NF-kappa B signaling pathway were all suppressed by both TNF-alpha and NF-kappa B inhibition. In order to verify the effect of PDTC on inflammatory response, we further explored its effect in vitro. Anti-inflammatory activity of PDTC was proved in U937 cell line. To conclude, both inhibitions of TNF-alpha and NF-kappa B are able to suppress the activation of TLR4 and NF-kappa B signaling pathway. However, NF-kappa B inhibition with PDTC failed to protect the rats in ACLF induced by d-Gal and LPS.

引用

页码：848 / 857

页数：10

共 33 条

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