Stimulator of interferon genes inhibitor alleviates lipopolysaccosis-induced mitochondrial apoptosis in hepatocytes
YAO Jie,FENG Zhi-peng
Department of Infectious Diseases, Taiyuan Central Hospital/The Ninth Clinical Medical College of Shanxi Medical University, Taiyua030009, China
Abstract:
Objective To explore the mechanism by which stimulator of interferon genes (STING) inhibitors regulate mitochondrial apoptosis induced by lipopolysaccharide in human hepatocytes. Methods Human hepatocytes (L02) were selected as the study object, and L02 cells were divided into control group, LPS group and LPS+STING inhibitor group by untreated treatment, LPS treatment and LPS combined with STING inhibitor treatment. Western blot was performed to detect the expression of STING signaling related proteins STING, TBK1, IRF3, the expression of mitochondrial apoptosis-related proteins Bcl-2, Bax and Caspase-3. The apoptosis rate was determined by flow cytometry and IL-1β and IL-18 levels were detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group, the levels of IL-1β and IL-18 in the supernatant and the apoptosis rate of L02 cells were increased in L02 cells after LPS treatment. However, after treatment with STING inhibitors, the cell apoptosis rate decreased, as well as the levels of IL-1β and IL-18 levels. In addition, the expression of STING, TBK1, IRF3, Bax and Caspase-3 were increased after LPS treatment, while the expression of Bcl-2 was decreased. Nevertheless, after treatment with STING inhibitors, the expression of STING, TBK1, IRF3, Bax and Caspase-3 were decreased, and the expression of Bcl-2 was increased. Conclusion Deactivating the STING signaling pathway can reduce the inflammatory response and mitochondrial apoptosis induced by LPS, thereby alleviating LPS-induced liver injury.
