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Int. J. Mol. Sci. 2015, 16(4), 7057-7076; doi:10.3390/ijms16047057

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

1
Department of Clinical Research, University of Bern, Bern 3010, Switzerland
2
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern 3012, Switzerland
3
Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern 3010, Switzerland
4
Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern 3010, Switzerland
5
Department of Nephrology, Inselspital, University of Bern, Bern 3010, Switzerland
6
Department of Medicine II, Division of Gastroenterology, University of Dresden, Dresden 01307, Germany
7
Department of Visceral Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Tatsuo Kanda
Received: 20 January 2015 / Revised: 6 March 2015 / Accepted: 23 March 2015 / Published: 27 March 2015
(This article belongs to the Special Issue Viral Hepatitis Research)
View Full-Text   |   Download PDF [1175 KB, uploaded 27 March 2015]   |  

Abstract

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. View Full-Text
Keywords: endocannabinoid system; hepatitis C; peripheral blood mononuclear cells; inflammation; fibrosis; liver endocannabinoid system; hepatitis C; peripheral blood mononuclear cells; inflammation; fibrosis; liver
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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.

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