期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 16, 期 4, 页码 7057-7076出版社
MDPI
DOI: 10.3390/ijms16047057
关键词
endocannabinoid system; hepatitis C; peripheral blood mononuclear cells; inflammation; fibrosis; liver
资金
- Swiss Foundation for Alcohol Research
- Swiss National Science Foundation [3100 A0-122114/1]
- Roche and Merck Sharp Dohme (MSD)
- Gertrud and Walter Siegenthaler Foundation, Zurich, Switzerland
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 [H-3]AEA and [H-3]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-, TNF-, 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.
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