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

International Journal of Molecular Sciences

Eleonora Patsenker⁷  Philip Sachse⁷  Andrea Chicca³  Mar໚ Salomé Gachet³  Vreni Schneider⁷  Johan Mattsson⁵  Christian Lanz⁵  Mathias Worni²  Andrea de Gottardi²  Mariam Semmo¹  Jochen Hampe⁶  Clemens Schafmayer⁴  Rudolf Brenneisen⁵  Jürg Gertsch³  Felix Stickel⁷  Nasser Semmo⁷ 

[1] Department of Nephrology, Inselspital, University of Bern, Bern 3010, Switzerland; E-Mail:;Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern 3010, Switzerland; E-Mails:;Institute of Biochemistry and Molecular Medicine, University of Bern, Bern 3012, Switzerland; E-Mails:;Department of Visceral Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany; E-Mail:;Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern 3010, Switzerland; E-Mails:;Department of Medicine II, Division of Gastroenterology, University of Dresden, Dresden 01307, Germany; E-Mail:;Department of Clinical Research, University of Bern, Bern 3010, Switzerland; E-Mails:

关键词: endocannabinoid system;    hepatitis C;    peripheral blood mononuclear cells;    inflammation;    fibrosis;    liver;   

DOI  :  10.3390/ijms16047057

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.