期刊
CELL AND TISSUE RESEARCH
卷 336, 期 1, 页码 67-77出版社
SPRINGER
DOI: 10.1007/s00441-009-0751-8
关键词
Barrier; Claudin-2; Phosphatidylinositol-3-kinase; Tight junction; TNF alpha; Human
类别
资金
- Detlef Sorgenfrei (electronic engineer)
Our aim has been to characterize the molecular mechanisms regulating the expression of the channel-forming tight-junctional protein claudin-2 in response to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF alpha), which is elevated, for example, in active Crohn's disease. TNF alpha caused an 89% decrease of the paracellular resistance in colonic HT-29/B6 cells, whereas transcellular resistance was unaltered. The claudin-2 protein level was increased by TNF alpha without changes in subcellular tight-junctional protein localization as revealed by confocal laser scanning microscopy. Enhanced gene expression was identified as the source of this increase, since claudin-2-specific mRNA and promoter activity was elevated, whereas mRNA stability remained unaltered. Specific inhibitors and phospho-specific antibodies revealed that the increased gene expression of claudin-2 after TNF alpha treatment was mediated by the phosphatidylinositol-3-kinase pathway. Thus, the up-regulation of claudin-2 by TNF alpha is attributable to the regulation of the expression of the gene, as a result of which epithelial barrier function is disturbed, for example, during chronic intestinal inflammation.
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