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pubmed-article:19128033pubmed:abstractTextInterferon-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.lld:pubmed
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pubmed-article:19128033pubmed:authorpubmed-author:KennedyJohn...lld:pubmed
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pubmed-article:19128033pubmed:volume29lld:pubmed
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pubmed-article:19128033pubmed:pagination45-54lld:pubmed
pubmed-article:19128033pubmed:dateRevised2011-3-1lld:pubmed
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pubmed-article:19128033pubmed:year2009lld:pubmed
pubmed-article:19128033pubmed:articleTitleMechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction.lld:pubmed
pubmed-article:19128033pubmed:affiliationDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-5271, USA.lld:pubmed
pubmed-article:19128033pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:19128033pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
pubmed-article:19128033pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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