Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis
- M V Aptea,
- P S Habera,
- S J Darbya,
- S C Rodgersa,
- G W McCaughana,
- M A Korstenb,
- R C Pirolaa,
- J S Wilsona
- aPancreatic Research Group, Department of Gastroenterology, Prince of Wales Hospital and University of New South Wales, Sydney, Australia, bMount Sinai School of Medicine, New York, USA
- Associate Professor J S Wilson, Department of Gastroenterology, Edmund Blacket Building, Prince of Wales Hospital, Randwick NSW 2031, Australia.
- Accepted 21 October 1998
BACKGROUND The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells play a major role in fibrogenesis by synthesising increased amounts of collagen and other extracellular matrix (ECM) proteins when activated by profibrogenic mediators such as cytokines and oxidant stress.
AIMS To determine whether cultured rat pancreatic stellate cells produce collagen and other ECM proteins, and exhibit signs of activation when exposed to the cytokines platelet derived growth factor (PDGF) or transforming growth factor β (TGF-β).
METHODS Cultured pancreatic stellate cells were immunostained for the ECM proteins procollagen III, collagen I, laminin, and fibronectin using specific polyclonal antibodies. For cytokine studies, triplicate wells of cells were incubated with increasing concentrations of PDGF or TGF-β.
RESULTS Cultured pancreatic stellate cells stained strongly positive for all ECM proteins tested. Incubation of cells with 1, 5, and 10 ng/ml PDGF led to a significant dose related increase in cell counts as well as in the incorporation of3H-thymidine into DNA. Stellate cells exposed to 0.25, 0.5, and 1 ng/ml TGF-β showed a dose dependent increase in α smooth muscle actin expression and increased collagen synthesis. In addition, TGF-β increased the expression of PDGF receptors on stellate cells.
CONCLUSIONS Pancreatic stellate cells produce collagen and other extracellular matrix proteins, and respond to the cytokines PDGF and TGF-β by increased proliferation and increased collagen synthesis. These results suggest an important role for stellate cells in pancreatic fibrogenesis.
- extracellular matrix
- glial fibrillary acidic protein
- platelet derived growth factor
- platelet derived growth factor receptor
- smooth muscle actin
- transforming growth factor
- Fisher’s protected least significant difference test