Regulation of the hepatic and pancreatic stellate cell by Interferon alpha
Regulation of the hepatic and pancreatic stellate cell by Interferon alpha
I hypothesized that Interferon alpha ameliorates liver fibrosis by the downregulating central aspects of the activated HSC. In addition, stellate cells isolated from the pancreas were studied to compare their activated phenotype with that of the HSC. Hepatic and pancreatic stellate cells were also treated with Interferon alpha to study whether a common response to Interferon alpha could be demonstrated.
At 72 hours, Interferon alpha downregulated the production of alpha smooth muscle actin in cultured HSC. However, no effect was observed on the expression of MMP-2, MMP-9 and collagen-L. As analysed by Acridine Orange, apoptosis was unaffected, but by 3H Thymidine incorporation treatment of hepatic stellate cells with Interferon alpha significantly reduced proliferation and was statistically significant. This was confirmed with assessment of total DNA and activation of ERK1 and ERK2 by western blotting.
To further determine the effects of Interferon alpha, an in vivo model was studied to evaluate the effect of therapy on an established liver fibrosis following carbon tetrachloride treatment. A statistically significant decrease in fibrosis was observed in rats treated with Interferon alpha relative to control treated with carbon tetrachloride treatment alone. In addition there was a reduction in alpha smooth muscle actin staining in sections of treated liver. Treated animals also demonstrated a reduction in ascites. Other parameters assessed demonstrated no significant changes between the untreated and treated groups.
Therefore the antifibrotic effects of Interferon alpha may be due to antiproliferative properties. Interferon alpha may only modestly regulate the phenotype of the activated stellate cell but may enhance the reduction in fibrosis possibly through decreasing stellate cell proliferation. Furthermore, I have demonstrated a common mechanism between two stellate cells when activated, adding to work in this area.
University of Southampton
Walker, Fiona Mairi Joyce
f4fbdec7-b351-4a05-988c-6626a1943b0e
2003
Walker, Fiona Mairi Joyce
f4fbdec7-b351-4a05-988c-6626a1943b0e
Walker, Fiona Mairi Joyce
(2003)
Regulation of the hepatic and pancreatic stellate cell by Interferon alpha.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
I hypothesized that Interferon alpha ameliorates liver fibrosis by the downregulating central aspects of the activated HSC. In addition, stellate cells isolated from the pancreas were studied to compare their activated phenotype with that of the HSC. Hepatic and pancreatic stellate cells were also treated with Interferon alpha to study whether a common response to Interferon alpha could be demonstrated.
At 72 hours, Interferon alpha downregulated the production of alpha smooth muscle actin in cultured HSC. However, no effect was observed on the expression of MMP-2, MMP-9 and collagen-L. As analysed by Acridine Orange, apoptosis was unaffected, but by 3H Thymidine incorporation treatment of hepatic stellate cells with Interferon alpha significantly reduced proliferation and was statistically significant. This was confirmed with assessment of total DNA and activation of ERK1 and ERK2 by western blotting.
To further determine the effects of Interferon alpha, an in vivo model was studied to evaluate the effect of therapy on an established liver fibrosis following carbon tetrachloride treatment. A statistically significant decrease in fibrosis was observed in rats treated with Interferon alpha relative to control treated with carbon tetrachloride treatment alone. In addition there was a reduction in alpha smooth muscle actin staining in sections of treated liver. Treated animals also demonstrated a reduction in ascites. Other parameters assessed demonstrated no significant changes between the untreated and treated groups.
Therefore the antifibrotic effects of Interferon alpha may be due to antiproliferative properties. Interferon alpha may only modestly regulate the phenotype of the activated stellate cell but may enhance the reduction in fibrosis possibly through decreasing stellate cell proliferation. Furthermore, I have demonstrated a common mechanism between two stellate cells when activated, adding to work in this area.
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Published date: 2003
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Local EPrints ID: 465149
URI: http://eprints.soton.ac.uk/id/eprint/465149
PURE UUID: 179432e0-80cb-4801-a730-5ca2d0ebd03c
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Date deposited: 05 Jul 2022 00:26
Last modified: 16 Mar 2024 19:59
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Author:
Fiona Mairi Joyce Walker
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