TNFα up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling

被引：132

作者：

Mankertz, J. ^{[2
]}

Amasheh, M. ^{[2
]}

Krug, S. M. ^{[3
]}

Fromm, A. ^{[3
]}

Amasheh, S. ^{[3
]}

Hillenbrand, B. ^{[2
]}

Tavalali, S. ^{[2
]}

Fromm, M. ^{[3
]}

Schulzke, J. D. ^{[1
,2
]}

机构：

[1] Charite Univ Med Berlin, Dept Gen Med, D-12200 Berlin, Germany

[2] Charite Univ Med Berlin, Dept Gastroenterol, D-12200 Berlin, Germany

[3] Charite Univ Med Berlin, Inst Clin Physiol, D-12200 Berlin, Germany

来源：

CELL AND TISSUE RESEARCH | 2009年 / 336卷 / 01期

关键词：

Barrier; Claudin-2; Phosphatidylinositol-3-kinase; Tight junction; TNF alpha; Human; TIGHT JUNCTION PROTEINS; NECROSIS-FACTOR-ALPHA; INFLAMMATORY-BOWEL-DISEASE; IFN-GAMMA; BARRIER DYSFUNCTION; INTERFERON-GAMMA; ULCERATIVE-COLITIS; CROHNS-DISEASE; INHIBITION; APOPTOSIS;

D O I：

10.1007/s00441-009-0751-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：67 / 77

页数：11

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