β-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition of TLR4/NF-κB signaling pathway-mediated inflammation in mice

AIM To study the role and the possible mechanism of beta-arrestin 2 in lipopolysaccharide (LPS)-induced liver injury in vivo and in vitro. METHODS Male beta-arrestin 2(+/+) and beta-arrestin 2(-/-) C57BL/6J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-kappa B signaling pathway. RESULTS Compared with wild-type mice, the beta-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of proinflammatory cytokines, including interleukin (IL)1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-10. Compared with the control group, pro-inflammatory cytokines (including IL-1 beta, IL-6, TNF-alpha, and IL-10) produced by RAW264.7 cells in the beta-arrestin 2 siRNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-kappa B signaling pathway, including phospho-I kappa B alpha and phosho-p65, were upregulated. CONCLUSION beta-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-kappa B signaling pathwaymediated inflammation.