Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins

被引：111

作者：

Capaldo, Christopher T. ^{[1
]}

Farkas, Attila E. ^{[1
]}

Hilgarth, Roland S. ^{[1
]}

Krug, Susanne M. ^{[3
,4
]}

Wolf, Mattie F. ^{[1
]}

Benedik, Jeremy K. ^{[1
]}

Fromm, Michael ^{[3
,4
]}

Koval, Michael ^{[2
]}

Parkos, Charles ^{[1
]}

Nusrat, Asma ^{[1
]}

机构：

[1] Emory Univ, Dept Pathol & Lab Med, Epithelial Pathobiol & Mucosal Inflammat Res Unit, Atlanta, GA 30322 USA

[2] Emory Univ, Dept Cell Biol, Div Pulm Allergy & Crit Care Med, Atlanta, GA 30322 USA

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

[4] Humboldt Univ, D-12200 Berlin, Germany

来源：

MOLECULAR BIOLOGY OF THE CELL | 2014年 / 25卷 / 18期

基金：

美国国家卫生研究院;

关键词：

EPITHELIAL BARRIER FUNCTION; INFLAMMATORY-BOWEL-DISEASE; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; HUMAN CYTOMEGALOVIRUS; ZONULAE-OCCLUDENTES; ULCERATIVE-COLITIS; CELL-LINE; EXPRESSION; PERMEABILITY;

D O I：

10.1091/mbc.E14-02-0773

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Tight junctions (TJs) are dynamic, multiprotein intercellular adhesive contacts that provide a vital barrier function in epithelial tissues. TJs are remodeled during physiological development and pathological mucosal inflammation, and differential expression of the claudin family of TJ proteins determines epithelial barrier properties. However, the molecular mechanisms involved in TJ remodeling are incompletely understood. Using acGFP-claudin 4 as a biosensor of TJ remodeling, we observed increased claudin 4 fluorescence recovery after photobleaching (FRAP) dynamics in response to inflammatory cytokines. Interferon. and tumor necrosis factor a increased the proportion of mobile claudin 4 in the TJ. Up-regulation of claudin 4 protein rescued these mobility defects and cytokine-induced barrier compromise. Furthermore, claudins 2 and 4 have reciprocal effects on epithelial barrier function, exhibit differential FRAP dynamics, and compete for residency within the TJ. These findings establish a model of TJs as self-assembling systems that undergo remodeling in response to proinflammatory cytokines through a mechanism of heterotypic claudin-binding incompatibility.

引用

页码：2710 / 2719

页数：10

共 43 条

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