Novel roles of lipopolysaccharide and TLR4/NF-κB signaling pathway in inflammatory response to liver injury in Budd-Chiari syndrome

BACKGROUND Budd-Chiari syndrome (BCS) is an uncommon disorder characterized by obstruction of hepatic venous outflow. To date, the exact mechanism underlying hepatic injury derived from the hepatic venous outflow obstruction in BCS remains largely unknown. AIM To assess the role of NF-kappa B-mediated inflammation in BCS-induced liver injury in humans and rats. METHODS A total of 180 rats were randomly assigned into nine groups, including four BCS model groups (1, 3, 6 and 12 wk), four sham-operated groups (1, 3, 6 and 12 wk), and a control group. Lipopolysaccharide (LPS) levels in each group were detected by the Tachypleus Amebocyte Lysate assay. The mRNA and protein levels of TLR4, NF-kappa B, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2 and interferon (IFN)-gamma were quantified. In addition, 60 patients with BCS and 30 healthy controls were enrolled, and their blood samples were analyzed. RESULTS Hepatic and plasma LPS levels were significantly increased in rats. The mRNA and protein expression levels of TLR4, NF-kappa B and inflammatory cytokines (TNF-alpha, IL-2 and IFN-gamma) in liver tissues were significantly higher in the BCS model groups compared with the other two groups. In addition, the model groups (1, 3, 6 and 12 wk after BCS induction) showed significant differences in the levels of LPS, TLR4, NF-kappa B, TNF-alpha, IL-2 and IFN-gamma. Notably, there was a significant correlation between the LPS concentrations and mRNA and protein levels of TLR4, NF-kappa B and inflammatory cytokines. Importantly, it was revealed that the levels of LPS, TLR4, NF-kappa B and inflammatory cytokines were significantly greater in chronic BCS patients than healthy controls and acute BCS patients. CONCLUSION LPS level is markedly elevated in BCS, in turn activating the TLR4/NF-kappa B signaling pathway, leading to induction of inflammatory cytokines (TN F-alpha, IL-2 and IFN-gamma) in response to BCS-induced liver injury.

Automated summary

The study found that LPS levels were significantly elevated in BCS model groups, leading to increased expression of TLR4, NF-kappa B, and inflammatory cytokines in liver tissues. Importantly, chronic BCS patients had significantly higher levels of LPS, TLR4, NF-kappa B, and inflammatory cytokines compared to healthy controls and acute BCS patients.