Activation of hepatic stellate cells (HSCs) is a common cause of liver fibrosis. The activation is induced by various inflammatory mediators during liver injury. PGE₂, the main eicosanoid, is produced by Kupffer cells, hepatocytes and HSCs in the liver. In this study, we revealed the effect of PGE₂ on the activation of HSCs. Furthermore, we investigated the effect of inflammation on adenosine metabolism using diet-induced liver fibrosis model mice.
Mouse primary HSCs cultured by 10% FBS DMEM on plastic dishes and treated with reagents for 7days. HSC activation were evaluated by immunohistochemistry. Adenosine-related molecules were measured by qPCR in diet-induced liver fibrosis model mice.
PGE₂ had a progressive effect on HSC activation. On the other hand, PGE₂ strongly inhibited HSC activation only when an adenosine receptor antagonist, caffeine, is present; that is, adenosine receptor antagonists invert the effect of PGE₂ on HSC activation. So, we investigated adenosine-related genes in the model mice. The mRNA expression levels of extracellular adenosine synthases, nucleotide transporter, and adenosine deaminase were different between the model mice and normal mice.
             These results suggest the possibility that the alternations of adenosine-related genes progress HSC activation leading to liver fibrosis in inflammatory condition.