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

Abstract

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-κB-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-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-2 and interferon (IFN)-γ 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-κB and inflammatory cytokines (TNF-α, IL-2 and IFN-γ) 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-κB, TNF-α, IL-2 and IFN-γ. Notably, there was a significant correlation between the LPS concentrations and mRNA and protein levels of TLR4, NF-κB and inflammatory cytokines. Importantly, it was revealed that the levels of LPS, TLR4, NF-κB 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-κB signaling pathway, leading to induction of inflammatory cytokines (TNF-α, IL-2 and IFN-γ) in response to BCS-induced liver injury.

Knockdown of protein interacting with C α kinase 1 aggravates sepsis-induced acute liver injury by regulating the TLR4/NF-κB pathway

“…This result was supported by the finding of our study, which demonstrated that PICK1 inhibited the TLR4/NF-B pathway activation in the CLP sepsis-induced liver injury mouse model, which protected against sepsis-induced ALI. The TLR4/NF-κB pathway has been implicated in protecting the liver in multiple investigations 28 – 32 , which is consistent with the findings of our study. By observing the livers of mice, the severity of liver injury in the sepsis-induced liver injury mouse model was found to be highest in mice with PICK1 knockout.…”

Investigation of Correlation between Resistance to Diazepam and Expression of Inflammatory Markers in The Peripheral Blood of Patients with Status of Epilepticus

“…Furthermore, TLR4 gene expression might be influenced by several things such as age, stimulus, environtment or patient’s condition and cell part/type ( 63 ). The TLR4-dependent NF-–B signaling pathway is the primary pathway through which LPS induces an inflammatory response ( 44 , 64 ). TLR4-independent host response to LPS has also been identified ( 65 ).…”