The expression and function of interleukin-10 in liver injury
The expression and function of interleukin-10 in liver injury
Having shown that IL-10 is expressed in vivo in the course of liver injury and in activated KC, the effects of recombinant IL-10 on KC function in vitro were examined. IL-10 was able to inhibit the production of both tumour necrosis factor-alpha, and superoxide by rat KC and it did so much more consistently than either IL-13 or a related cytokine, IL-4.
The potential role of IL-10 in the control of matrix production and fibrosis in the liver was then addressed. Hepatic stellate cells (HSC) are responsible for the control of hepatic matrix turnover in the liver, a dynamic process which is disrupted during the development of cirrhosis. Pivotal to this is the activation of HSC and their transformation to myofibroblastic phenotype, a process which can be mimicked in vitro by culture of HSC on plastic. Using this model, IL-10 mRNA and protein were found to be up-regulated as cells became activated. HSC also released IL-10 protein into culture media after activation.
The expression of IL-10 by HSC upon activation may therefore influence the development of liver fibrosis. Genetically modified mice unable to express IL-10 were treated with CC14 and resultant hepatic fibrosis assessed histologically. Changes were compared with those in normal wild type animals, and with those unable to express either IL-4 or the matrix metalloproteinase inhibitor TIMP-1. Animals in which IL-10 or IL-4 were absent developed more advanced hepatic fibrosis than either TIMP-1-deleted animals or wild type controls.
In summary, these studies have shown that IL-10 is expressed by KC and by HSC, both of which are central to the generation of inflammation and fibrosis in the liver. Moreover, IL-10 is able to inhibit KC pro-inflammatory responses and its absence results in more advanced fibrosis in response to a hepatotoxin. It may, therefore, play a pivotal role, providing potential for therapeutic intervention in the modification of disease processes which result in hepatic cirrhosis.
University of Southampton
1998
Thompson, Kerry Coral
(1998)
The expression and function of interleukin-10 in liver injury.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Having shown that IL-10 is expressed in vivo in the course of liver injury and in activated KC, the effects of recombinant IL-10 on KC function in vitro were examined. IL-10 was able to inhibit the production of both tumour necrosis factor-alpha, and superoxide by rat KC and it did so much more consistently than either IL-13 or a related cytokine, IL-4.
The potential role of IL-10 in the control of matrix production and fibrosis in the liver was then addressed. Hepatic stellate cells (HSC) are responsible for the control of hepatic matrix turnover in the liver, a dynamic process which is disrupted during the development of cirrhosis. Pivotal to this is the activation of HSC and their transformation to myofibroblastic phenotype, a process which can be mimicked in vitro by culture of HSC on plastic. Using this model, IL-10 mRNA and protein were found to be up-regulated as cells became activated. HSC also released IL-10 protein into culture media after activation.
The expression of IL-10 by HSC upon activation may therefore influence the development of liver fibrosis. Genetically modified mice unable to express IL-10 were treated with CC14 and resultant hepatic fibrosis assessed histologically. Changes were compared with those in normal wild type animals, and with those unable to express either IL-4 or the matrix metalloproteinase inhibitor TIMP-1. Animals in which IL-10 or IL-4 were absent developed more advanced hepatic fibrosis than either TIMP-1-deleted animals or wild type controls.
In summary, these studies have shown that IL-10 is expressed by KC and by HSC, both of which are central to the generation of inflammation and fibrosis in the liver. Moreover, IL-10 is able to inhibit KC pro-inflammatory responses and its absence results in more advanced fibrosis in response to a hepatotoxin. It may, therefore, play a pivotal role, providing potential for therapeutic intervention in the modification of disease processes which result in hepatic cirrhosis.
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Published date: 1998
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Local EPrints ID: 463612
URI: http://eprints.soton.ac.uk/id/eprint/463612
PURE UUID: d7f7e766-b11e-4dc8-8fa6-112224c42312
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Date deposited: 04 Jul 2022 20:54
Last modified: 04 Jul 2022 20:54
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Author:
Kerry Coral Thompson
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