Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells.
<h4>Background</h4>While cannabinoids have been shown to ameliorate liver fibrosis, their effects in chronic pancreatitis and on pancreatic stellate cells (PSC) are unknown.<h4>Methodology/principal findings</h4>The activity of the endocannabinoid system was evaluated in huma...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-02-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001701&type=printable |
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| author | Christoph W Michalski Milena Maier Mert Erkan Danguole Sauliunaite Frank Bergmann Pal Pacher Sandor Batkai Nathalia A Giese Thomas Giese Helmut Friess Jörg Kleeff |
| author_facet | Christoph W Michalski Milena Maier Mert Erkan Danguole Sauliunaite Frank Bergmann Pal Pacher Sandor Batkai Nathalia A Giese Thomas Giese Helmut Friess Jörg Kleeff |
| author_sort | Christoph W Michalski |
| collection | DOAJ |
| description | <h4>Background</h4>While cannabinoids have been shown to ameliorate liver fibrosis, their effects in chronic pancreatitis and on pancreatic stellate cells (PSC) are unknown.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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. |
| format | Article |
| id | doaj-art-7dc41f53ca2a46a8a38ec6634c6f9e69 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7dc41f53ca2a46a8a38ec6634c6f9e692025-08-20T02:17:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-02-0132e170110.1371/journal.pone.0001701Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells.Christoph W MichalskiMilena MaierMert ErkanDanguole SauliunaiteFrank BergmannPal PacherSandor BatkaiNathalia A GieseThomas GieseHelmut FriessJörg Kleeff<h4>Background</h4>While cannabinoids have been shown to ameliorate liver fibrosis, their effects in chronic pancreatitis and on pancreatic stellate cells (PSC) are unknown.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001701&type=printable |
| spellingShingle | Christoph W Michalski Milena Maier Mert Erkan Danguole Sauliunaite Frank Bergmann Pal Pacher Sandor Batkai Nathalia A Giese Thomas Giese Helmut Friess Jörg Kleeff Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells. PLoS ONE |
| title | Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells. |
| title_full | Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells. |
| title_fullStr | Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells. |
| title_full_unstemmed | Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells. |
| title_short | Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells. |
| title_sort | cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001701&type=printable |
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