Background: It is now generally accepted that chronic pancreatic injury and fibrosis may result from repeated episodes of acute pancreatic necroinflammation (the necrosis-fibrosis sequence). Recent studies suggest that pancreatic stellate cells (PSCs), when activated, may play an important role in the development of pancreatic fibrosis. Factors that may influence PSC activation during pancreatic necroinflammation include cytokines known to be important in the pathogenesis of acute pancreatitis, such as tumour necrosis factor α (TNF-α), and the interleukins 1, 6, and 10 (IL-1, IL-6, and IL-10).
Aim: To determine the effects of these cytokines on PSC activation, as assessed by cell proliferation, α smooth muscle actin (α-SMA) expression, and collagen synthesis.
Methods: Cultured rat PSCs were incubated with cytokines for 24 hours. Cell proliferation was assessed by measuring 3H thymidine incorporation into cellular DNA, α-SMA expression by western blotting, and collagen synthesis by incorporation of 14C proline into collagenase sensitive protein. mRNA levels for procollagen α1(1) in PSCs were determined by northern and dot blotting methods.
Results: Expression of α-SMA by PSCs was increased on exposure to each of the cytokines used in the study. Stellate cell proliferation was stimulated by TNF-α but inhibited by IL-6, while IL-1 and IL-10 had no effect on PSC proliferation. Collagen synthesis by PSCs was stimulated by TNF-α and IL-10, inhibited in response to IL-6, and unaltered by IL-1. Changes in collagen protein synthesis in response to TNF-α, IL-10, and IL-6 were not regulated at the mRNA level in the cells.
Conclusion: This study has demonstrated that PSCs have the capacity to respond to cytokines known to be upregulated during acute pancreatitis. Persistent activation of PSCs by cytokines during acute pancreatitis may be a factor involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis.
- stellate cells
- α-SMA, α smooth muscle actin
- GAPDH, glyceraldehyde phosphate dehydrogenase
- IL, interleukin
- PDGF, platelet derived growth factor
- PSC, pancreatic stellate cell
- SDS, sodium dodecyl sulphate
- TCA, trichloroacetic acid
- TNF-α, tumour necrosis factor α
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