Source:http://linkedlifedata.com/resource/pubmed/id/19128033
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2009-1-8
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pubmed:abstractText |
Interferon-gamma (IFN-gamma) is an important proinflammatory cytokine that plays a central role in the intestinal inflammatory process of inflammatory bowel disease. IFN-gamma induced disturbance of the intestinal epithelial tight junction (TJ) barrier has been postulated to be an important mechanism contributing to intestinal inflammation. The intracellular mechanisms that mediate the IFN-gamma induced increase in intestinal TJ permeability remain unclear. The aim of this study was to examine the role of the phosphatidylinositol 3-kinase (PI3-K) pathway in the regulation of the IFN-gamma induced increase in intestinal TJ permeability using the T84 intestinal epithelial cell line. IFN-gamma caused an increase in T84 intestinal epithelial TJ permeability and depletion of TJ protein, occludin. The IFN-gamma induced increase in TJ permeability and alteration in occludin protein was associated with rapid activation of PI3-K; and inhibition of PI3-K activation prevented the IFN-gamma induced effects. IFN-gamma also caused a delayed but more prolonged activation of nuclear factor-kappaB (NF-kappaB); inhibition of NF-kappaB also prevented the increase in T84 TJ permeability and alteration in occludin expression. The IFN-gamma induced activation of NF-kappaB was mediated by a cross-talk with PI3-K pathway. In conclusion, the IFN-gamma induced increase in T84 TJ permeability and alteration in occludin protein expression were mediated by the PI3-K pathway. These results show for the first time that the IFN-gamma modulation of TJ protein and TJ barrier function is regulated by a cross-talk between PI3-K and NF-kappaB pathways.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/occludin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1557-7465
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45-54
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pubmed:dateRevised |
2011-3-1
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pubmed:meshHeading |
pubmed-meshheading:19128033-Antiviral Agents,
pubmed-meshheading:19128033-Cell Line,
pubmed-meshheading:19128033-Humans,
pubmed-meshheading:19128033-Interferon-gamma,
pubmed-meshheading:19128033-Intestinal Mucosa,
pubmed-meshheading:19128033-Membrane Proteins,
pubmed-meshheading:19128033-NF-kappa B,
pubmed-meshheading:19128033-Permeability,
pubmed-meshheading:19128033-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19128033-Tight Junctions
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pubmed:year |
2009
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pubmed:articleTitle |
Mechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction.
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pubmed:affiliation |
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-5271, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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