A20 Attenuates Lipopolysaccharide-Induced Inflammation Through MAPK/ERK/JNK Pathway in LX-2 Cells

Background: Hepatic stellate cells (HSCs) are liver-specific pericytes that transform into myofibroblasts, which are involved in pathological vascularization in liver fibrosis. We previously suggested that A20 overexpression suppresses lipopolysaccharide (LPS)induced inflammation in HSC. We aimed to determine the mechanisms of the anti-inflammatory role of A20 in LX-2 cells. Methods: LX-2 cells were transfected with A20-siRNA or control-siRNA and control adenovirus or A20-carrying adenovirus. Quantitative reverse transcription PCR (RT-qPCR) analysis was employed to quantify mRNA levels of alpha-SMA, col-I, col-III, IL-6, TGF-0, and PDGF in A20-siRNA LX-2 cells stimulated with LPS. Multiple molecular indices of MAPK/ERK/JNK signal pathway were performed by using Western blotting. Results: Relative to control, the fibrosis-related mRNA levels of alpha-SMA, col-I, and col-III were increased in A20-siRNA LX-2 cells. Meanwhile, A20-siRNA cells significantly increased IL-6, TGF-0, and PDGF mRNA levels. Relative to controls, stimulating A20 overexpressing LX-2 cells with LPS for 5 and 30 minutes significantly reduced the levels of phosphorylated ERK and JNK, respectively. A20 knockdown in LX-2 cells promotes phosphorylated ERK and JNK levels with LPS for 30 minutes. Conclusions: Our data indicate that A20 could be functional in HSCs through the MAPK/ERK/JNK signaling pathway, highlighting a potential novel therapeutic strategy against liver fibrosis.