Abstract
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-α polyclonal antibody (as TNF-α inhibitor) and pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor) were used to treat the liver failure animals, respectively. The results showed that TNF-α inhibition was beneficial, but NF-κB inhibition failed to protect the rats in ACLF. However, HMGB1 levels, cytokine production and activation of TLR4-NF-κB signaling pathway were all suppressed by both TNF-α and NF-κB 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-α and NF-κB are able to suppress the activation of TLR4 and NF-κB signaling pathway. However, NF-κB inhibition with PDTC failed to protect the rats in ACLF induced by d-Gal and LPS.
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Acknowledgement
This study was supported by a grant from the National Natural Science Foundation of China (No. 81071342 and 81371789).
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Yang, F., Li, X., Wang, Lk. et al. 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. Inflammation 37, 848–857 (2014). https://doi.org/10.1007/s10753-013-9805-x
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DOI: https://doi.org/10.1007/s10753-013-9805-x