Cannabinoid 1 receptor (CB1R) expression is upregulated in the liver with viral hepatitis, cirrhosis, and both alcoholic and non-alcoholic fatty liver disease (FLD), whereas its expression is muted under usual physiological conditions. Inhibiting CB1R has been shown to be beneficial in preserving hepatic function in FLD but it is unclear if inhibiting CB1R during an inflammatory response to an acute hepatic injury, such as toxin-induced injury, would also be beneficial. We found that intrinsic CB1R in hepatocytes regulated liver inflammation-related gene transcription. We tested if nullification of hepatocyte-specific CB1R (hCNR1) in mice protects against concanavalin A (Con A)-induced liver injury. We looked for evidence of liver damage and markers of inflammation in response to Con A by measuring liver enzyme levels and proinflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, IL-17) in serum collected from hCNR1 and control mice. We observed a shift to the right in the dose-response curve for liver injury and inflammation in hCNR1 mice. We also found less inflammatory cell infiltration and focal necrosis in livers of hCNR1 mice compared to controls, resulting from downregulated apoptotic markers. This anti-apoptotic mechanism results from increased activation of nuclear factor kappa B (NF-κB), especially cAMP-dependent cannabinoid signaling and membrane-bound TNF-α, via downregulated TNF-α receptor 2 (TNFR2) transcription levels. Collectively, these findings provide insight into involvement of CB1R in the pathogenesis of acute liver injury.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726564PMC
http://dx.doi.org/10.1038/s41419-020-03261-8DOI Listing

Publication Analysis

Top Keywords

hcnr1 mice
12
liver injury
12
liver
9
cannabinoid receptor
8
liver damage
8
inhibiting cb1r
8
cb1r
6
injury
5
hepatocyte cannabinoid
4
receptor nullification
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!