Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation

• Published in: International journal of molecular sciences Vol. 16; no. 4; pp. 7057 - 7076
• Main Authors: Patsenker, Eleonora, Sachse, Philip, Chicca, Andrea, Gachet, María, Schneider, Vreni, Mattsson, Johan, Lanz, Christian, Worni, Mathias, De Gottardi, Andrea, Semmo, Mariam, Hampe, Jochen, Schafmayer, Clemens, Brenneisen, Rudolf, Gertsch, Jürg, Stickel, Felix, Semmo, Nasser
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.03.2015; MDPI
• Subjects: Adult; Amidohydrolases - metabolism; Arachidonic Acids - blood; Arachidonic Acids - metabolism; Cells, Cultured; Cellular biology; Cytokines - metabolism; Endocannabinoids - blood; Endocannabinoids - metabolism; Female; Glycerides - blood; Glycerides - metabolism; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - pathology; Hepatitis; Hepatitis C virus; Hepatitis C, Chronic - enzymology; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - pathology; Humans; Immune system; Immunity, Cellular; Liver; Male; Marijuana; Middle Aged; Monoacylglycerol Lipases - metabolism; Polyunsaturated Alkamides - blood; Polyunsaturated Alkamides - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms16047057

The endocannabinoid (EC) system is implicated in many chronic liver diseases, including hepatitis C viral (HCV) infection. Cannabis consumption is associated with fibrosis progression in patients with chronic hepatitis C (CHC), however, the role of ECs in the development of CHC has never been explored. To study this question, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were quantified in samples of HCV patients and healthy controls by gas and liquid chromatography mass spectrometry. Fatty acid amide hydrolase (FAAH) and monoaclyglycerol lipase (MAGL) activity was assessed by [3H]AEA and [3H]2-AG hydrolysis, respectively. Gene expression and cytokine release were assayed by TaqMan PCR and ELISpot, respectively. AEA and 2-AG levels were increased in plasma of HCV patients, but not in liver tissues. Hepatic FAAH and MAGL activity was not changed. In peripheral blood mononuclear cells (PBMC), ECs inhibited IFN-γ, TNF-α, and IL-2 secretion. Inhibition of IL-2 by endogenous AEA was stronger in PBMC from HCV patients. In hepatocytes, 2-AG induced the expression of IL-6, -17A, -32 and COX-2, and enhanced activation of hepatic stellate cells (HSC) co-cultivated with PBMC from subjects with CHC. In conclusion, ECs are increased in plasma of patients with CHC and might reveal immunosuppressive and profibrogenic effects.