International Journal of Molecular Sciences | |
Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation | |
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】
CC BY
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
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