title: Elevated levels of endocannabinoids in chronic hepatitis C may modulate cellular immune response and hepatic stellate cell activation.
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.
authors.affiliation: Department of Clinical Research, University of Bern, Bern 3010, Switzerland. eleonora.patsenker@ikp.unibe.ch.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Patsenker
authors.affiliation: Department of Clinical Research, University of Bern, Bern 3010, Switzerland. sachsephilip@gmail.com.
authors.forename: Philip
authors.initials: P
authors.lastname: Sachse
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bern 3012, Switzerland. andrea.chicca@ibmm.unibe.ch.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chicca
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bern 3012, Switzerland. maria.gachet@ibmm.unibe.ch.
authors.forename: María Salomé
authors.initials: MS
authors.lastname: Gachet
authors.affiliation: Department of Clinical Research, University of Bern, Bern 3010, Switzerland. vreni.schneider@ikp.unibe.ch.
authors.forename: Vreni
authors.initials: V
authors.lastname: Schneider
authors.affiliation: Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern 3010, Switzerland. Johan.Mattsson@insel.ch.
authors.forename: Johan
authors.initials: J
authors.lastname: Mattsson
authors.affiliation: Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern 3010, Switzerland. christian.lanz@dkf.unibe.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Lanz
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern 3010, Switzerland. christian.lanz@dkf.unibe.ch.
authors.forename: Mathias
authors.initials: M
authors.lastname: Worni
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern 3010, Switzerland. andrea.degottardi@ikp.unibe.ch.
authors.forename: Andrea
authors.initials: A
authors.lastname: de Gottardi
authors.affiliation: Department of Nephrology, Inselspital, University of Bern, Bern 3010, Switzerland. Mariam.Semmo@insel.ch.
authors.forename: Mariam
authors.initials: M
authors.lastname: Semmo
authors.affiliation: Department of Medicine II, Division of Gastroenterology, University of Dresden, Dresden 01307, Germany. jochen.hampe@uniklinikum-dresden.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.affiliation: Department of Visceral Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany. clemens.schafmayer@uksh-kiel.de.
authors.forename: Clemens
authors.initials: C
authors.lastname: Schafmayer
authors.affiliation: Department of Clinical Research, Laboratory of Phytopharmacology, Bioanalytics and Pharmacokinetics, University of Bern, Bern 3010, Switzerland. rudolf.brenneisen@dkf.unibe.ch.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Brenneisen
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bern 3012, Switzerland. juerg.gertsch@ibmm.unibe.ch.
authors.forename: Jürg
authors.initials: J
authors.lastname: Gertsch
authors.affiliation: Department of Clinical Research, University of Bern, Bern 3010, Switzerland. felix.stickel@ikp.unibe.ch.
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.affiliation: Department of Clinical Research, University of Bern, Bern 3010, Switzerland. nasser.semmo@insel.ch.|Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern 3010, Switzerland. nasser.semmo@insel.ch.
authors.forename: Nasser
authors.initials: N
authors.lastname: Semmo
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism; D001095:Arachidonic Acids / Q000097:blood / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D063388:Endocannabinoids / Q000097:blood / Q000378:metabolism*; D005260:Female; D005989:Glycerides / Q000097:blood / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000097:blood / Q000378:metabolism*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D016207:Cytokines; D063388:Endocannabinoids; D005989:Glycerides; D008994:Monoacylglycerol Lipases; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C078814:anandamide
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