Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells.
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.
Michalski
Christoph W
CW
Department of Surgery, Technische Universität München, Munich, Germany.
Maier
Milena
M
Erkan
Mert
M
Sauliunaite
Danguole
D
Bergmann
Frank
F
Pacher
Pal
P
Batkai
Sandor
S
Giese
Nathalia A
NA
Giese
Thomas
T
Friess
Helmut
H
Kleeff
Jörg
J
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*
D015415:Biomarkers; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids