Cannabinoid receptors as novel targets in the treatment of T cell-mediated fibrosis (96.26)

Liver diseases are one of the main causes of mortality in the world, especially chronic hepatitis leading to the development of liver cirrhosis or liver cancer. Previous studies have shown that natural cannabinoids such as Δ⁹-tetrahydrocannabinol (THC) exhibit immunosuppressive and anti-inflammatory properties. In this study, we investigated the effect of THC on chronic hepatitis caused by repeated toxic insult. For the chronic hepatitis, ConA or CCl₄ was administered to the C57BL/6 mice for several weeks. THC was injected after every toxic insult. Livers were collected for the histological assessment and hepatic cells were harvested for flow cytometric analysis to characterize the nature of hepatic inflammatory cells. Fibrosis related gene expression in injured liver was investigated by real time PCR. The results showed that THC treatment suppressed the mRNA expression of liver fibrosis markers and flow cytometric analysis suggested that THC treatment decreased the inflammatory cell accumulation in the liver in ConA-induced model. On the contrary, THC did not suppress the progression of fibrosis in CCl₄-induced model. Together, these results demonstrated that THC can suppress chronic autoimmune hepatitis but not chemical-induced hepatitis and that cannabinoid receptors can be the new therapeutic targets preventing immune cell-mediated liver injury (Supported in part by NIH grants R01AI053703, R01ES09098, R01 AI058300, R01DA016545, R01HL058641, R01ES019313 and P01AT003961)