title: Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells.
abstract: BACKGROUND
  While cannabinoids have been shown to ameliorate liver fibrosis, their effects in chronic pancreatitis and on pancreatic stellate cells (PSC) are unknown.
  
  
  RESULTS
  The activity of the endocannabinoid system was evaluated in human chronic pancreatitis (CP) tissues. In vitro, effects of blockade and activation of cannabinoid receptors on pancreatic stellate cells were characterized. In CP, cannabinoid receptors were detected predominantly in areas with inflammatory changes, stellate cells and nerves. Levels of endocannabinoids were decreased compared with normal pancreas. Cannabinoid-receptor-1 antagonism effectuated a small PSC phenotype and a trend toward increased invasiveness. Activation of cannabinoid receptors, however, induced de-activation of PSC and dose-dependently inhibited growth and decreased IL-6 and MCP-1 secretion as well as fibronectin, collagen1 and alphaSMA levels. De-activation of PSC was partially reversible using a combination of cannabinoid-receptor-1 and -2 antagonists. Concomitantly, cannabinoid receptor activation specifically decreased invasiveness of PSC, MMP-2 secretion and led to changes in PSC phenotype accompanied by a reduction of intracellular stress fibres.
  
  
  CONCLUSIONS
  Augmentation of the endocannabinoid system via exogenously administered cannabinoid receptor agonists specifically induces a functionally and metabolically quiescent pancreatic stellate cell phenotype and may thus constitute an option to treat inflammation and fibrosis in chronic pancreatitis.
authors.affiliation: Department of Surgery, Technische Universität München, Munich, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.forename: Milena
authors.initials: M
authors.lastname: Maier
authors.forename: Mert
authors.initials: M
authors.lastname: Erkan
authors.forename: Danguole
authors.initials: D
authors.lastname: Sauliunaite
authors.forename: Frank
authors.initials: F
authors.lastname: Bergmann
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
authors.forename: Sandor
authors.initials: S
authors.lastname: Batkai
authors.forename: Nathalia A
authors.initials: NA
authors.lastname: Giese
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
mesh_terms: D015415:Biomarkers; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids / Q000494:pharmacology*; D002478:Cells, Cultured; D005355:Fibrosis / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D010195:Pancreatitis / Q000188:drug therapy*
chemical_list: D015415:Biomarkers; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids