The Protective Roles of IL-6 Trans-Signaling Regulated by ADAM9 on the Liver in Carbon Tetrachloride-Induced Liver Injury in Mice.

ABSTRACT

Our study was undertaken to evaluate the important role that a disintegrin and metalloproteinase 9 (ADAM9) regulates IL-6 trans-signaling in carbon tetrachloride (CCl4)-induced liver injury in mice. Mice were divided into four groups. Each group respectively received mineral oil injection, CCl4 injection, anti-ADAM9 monoclonal antibody (mAb) pretreatment and CCl4 injection, anti-ADAM9 mAb and recombinant mouse ADAM9 molecules pretreatment with CCl4 injection. Our results showed that anti-ADAM9 mAb pretreatment significantly aggravated liver injury, inhibited IL-6 trans-signaling, which led to downregulation of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), upregulation of Caspase3, cytochrome P450 2E1 (CYP2E1), and hepatocytes apoptosis at 24 h after CCl4 injection. Recombinant ADAM9 molecules pretreatment reversed the impact of anti-ADAM9 mAb pretreatment in mice. In conclusion, our study suggested that ADAM9 could regulate the hepatocytes proliferation, apoptosis, angiogenesis, and CYP2E1 expression by activating IL-6 trans-signaling and play important protective roles during CCl4-induced liver injury in mice.