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Role of epithelial integrin-linked kinase in promoting intestinal inflammation: effects on CCL2, fibronectin and the T cell repertoire Assi, Kiran; Patterson, Scott; Dedhar, Shoukat; Owen, David; Levings, Megan; Salh, Baljinder
Abstract
Background: The role of integrin signaling in mucosal inflammation is presently unknown. Hence, we aimed to investigate the role of epithelial-derived integrin-linked kinase (ILK), a critical integrin signaling intermediary molecule, in colonic inflammation. Methods: Conditional intestinal epithelial cell ILK knockout mice were used for assessment of acute and chronic dextran sodium sulfate (DSS) -induced colitis. Disease activity was scored using standard histological scoring, mucosal cytokines were measured using ELISA, chemokines were determined using reverse-transcription polymerase chain reaction, as well as Q-PCR, and intracellular cytokine staining performed using FACS analysis. Results: In both acute and chronic DSS-induced colitis, compared to wild-type mice, ILK-ko mice exhibit less weight loss, and have reduced inflammatory scores. In an in vitro model system using HCT116 cells, we demonstrate that si-RNA mediated down-regulation of ILK results in a reduction in monocyte chemoattractant protein 1 (MCP1, CCL2) chemokine expression. A reduction in CCL2 levels is also observed in the tissue lysates of chronically inflamed colons from ILK-ko mice. Examination of mesenteric lymph node lymphocytes from ILK-ko mice reveals that there is a reduction in the levels of IFN gamma using intracellular staining, together with an increase in Foxp3+ T regulatory cells. Immunohistochemistry demonstrates that reduced fibronectin expression characterizes the inflammatory lesions within the colons of ILK-ko mice. Intriguingly, we demonstrate that fibronectin is directly capable of downregulating T regulatory cell development. Conclusions: Collectively, the data indicate for the first time that ILK plays a pro-inflammatory role in intestinal inflammation, through effects on chemokine expression, the extracellular matrix and immune tolerance.
Item Metadata
Title |
Role of epithelial integrin-linked kinase in promoting intestinal inflammation: effects on CCL2, fibronectin and the T cell repertoire
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Creator | |
Publisher |
BioMed Central
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Date Issued |
2011-08-01
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Description |
Background:
The role of integrin signaling in mucosal inflammation is presently unknown. Hence, we aimed to investigate the role of epithelial-derived integrin-linked kinase (ILK), a critical integrin signaling intermediary molecule, in colonic inflammation.
Methods:
Conditional intestinal epithelial cell ILK knockout mice were used for assessment of acute and chronic dextran sodium sulfate (DSS) -induced colitis. Disease activity was scored using standard histological scoring, mucosal cytokines were measured using ELISA, chemokines were determined using reverse-transcription polymerase chain reaction, as well as Q-PCR, and intracellular cytokine staining performed using FACS analysis.
Results:
In both acute and chronic DSS-induced colitis, compared to wild-type mice, ILK-ko mice exhibit less weight loss, and have reduced inflammatory scores. In an in vitro model system using HCT116 cells, we demonstrate that si-RNA mediated down-regulation of ILK results in a reduction in monocyte chemoattractant protein 1 (MCP1, CCL2) chemokine expression. A reduction in CCL2 levels is also observed in the tissue lysates of chronically inflamed colons from ILK-ko mice. Examination of mesenteric lymph node lymphocytes from ILK-ko mice reveals that there is a reduction in the levels of IFN gamma using intracellular staining, together with an increase in Foxp3+ T regulatory cells. Immunohistochemistry demonstrates that reduced fibronectin expression characterizes the inflammatory lesions within the colons of ILK-ko mice. Intriguingly, we demonstrate that fibronectin is directly capable of downregulating T regulatory cell development.
Conclusions:
Collectively, the data indicate for the first time that ILK plays a pro-inflammatory role in intestinal inflammation, through effects on chemokine expression, the extracellular matrix and immune tolerance.
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Subject | |
Genre | |
Type | |
Language |
eng
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Date Available |
2016-01-12
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution 4.0 International (CC BY 4.0)
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DOI |
10.14288/1.0223295
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URI | |
Affiliation | |
Citation |
BMC Immunology. 2011 Aug 01;12(1):42
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Publisher DOI |
10.1186/1471-2172-12-42
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Peer Review Status |
Reviewed
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Scholarly Level |
Faculty
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Copyright Holder |
Assi et al; licensee BioMed Central Ltd.
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Rights URI | |
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DSpace
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Rights
Attribution 4.0 International (CC BY 4.0)