International Journal of Molecular Sciences (2015-03-01)

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

  • Eleonora Patsenker,
  • Philip Sachse,
  • Andrea Chicca,
  • María Salomé Gachet,
  • Vreni Schneider,
  • Johan Mattsson,
  • Christian Lanz,
  • Mathias Worni,
  • Andrea de Gottardi,
  • Mariam Semmo,
  • Jochen Hampe,
  • Clemens Schafmayer,
  • Rudolf Brenneisen,
  • Jürg Gertsch,
  • Felix Stickel,
  • Nasser Semmo

DOI
https://doi.org/10.3390/ijms16047057
Journal volume & issue
Vol. 16, no. 4
pp. 7057 – 7076

Abstract

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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.

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