Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation
AbstractThe 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. View Full-Text
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Patsenker, E.; Sachse, P.; Chicca, A.; Gachet, M.S.; Schneider, V.; Mattsson, J.; Lanz, C.; Worni, M.; de Gottardi, A.; Semmo, M.; Hampe, J.; Schafmayer, C.; Brenneisen, R.; Gertsch, J.; Stickel, F.; Semmo, N. Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation. Int. J. Mol. Sci. 2015, 16, 7057-7076.
Patsenker E, Sachse P, Chicca A, Gachet MS, Schneider V, Mattsson J, Lanz C, Worni M, de Gottardi A, Semmo M, Hampe J, Schafmayer C, Brenneisen R, Gertsch J, Stickel F, Semmo N. Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation. International Journal of Molecular Sciences. 2015; 16(4):7057-7076.Chicago/Turabian Style
Patsenker, Eleonora; Sachse, Philip; Chicca, Andrea; Gachet, María S.; 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. 2015. "Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation." Int. J. Mol. Sci. 16, no. 4: 7057-7076.