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Int J Mol Sci. 2015 Mar 27;16(4):7057-76. doi: 10.3390/ijms16047057.

Elevated levels of endocannabinoids in chronic hepatitis C may modulate cellular immune response and hepatic stellate cell activation.

Author information

1
Department of Clinical Research, University of Bern, Bern 3010, Switzerland. eleonora.patsenker@ikp.unibe.ch.
2
Department of Clinical Research, University of Bern, Bern 3010, Switzerland. sachsephilip@gmail.com.
3
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern 3012, Switzerland. andrea.chicca@ibmm.unibe.ch.
4
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern 3012, Switzerland. maria.gachet@ibmm.unibe.ch.
5
Department of Clinical Research, University of Bern, Bern 3010, Switzerland. vreni.schneider@ikp.unibe.ch.
6
Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern 3010, Switzerland. Johan.Mattsson@insel.ch.
7
Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern 3010, Switzerland. christian.lanz@dkf.unibe.ch.
8
Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern 3010, Switzerland. christian.lanz@dkf.unibe.ch.
9
Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern 3010, Switzerland. andrea.degottardi@ikp.unibe.ch.
10
Department of Nephrology, Inselspital, University of Bern, Bern 3010, Switzerland. Mariam.Semmo@insel.ch.
11
Department of Medicine II, Division of Gastroenterology, University of Dresden, Dresden 01307, Germany. jochen.hampe@uniklinikum-dresden.de.
12
Department of Visceral Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany. clemens.schafmayer@uksh-kiel.de.
13
Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern 3010, Switzerland. rudolf.brenneisen@dkf.unibe.ch.
14
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern 3012, Switzerland. juerg.gertsch@ibmm.unibe.ch.
15
Department of Clinical Research, University of Bern, Bern 3010, Switzerland. felix.stickel@ikp.unibe.ch.
16
Department of Clinical Research, University of Bern, Bern 3010, Switzerland. nasser.semmo@insel.ch.
17
Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern 3010, Switzerland. nasser.semmo@insel.ch.

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.

PMID:
25826533
PMCID:
PMC4425004
DOI:
10.3390/ijms16047057
[Indexed for MEDLINE]
Free PMC Article

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