Regulation of the intestinal epithelial barrier by the apical junctional complex

被引:230
作者
Laukoetter, MG
Bruewer, M
Nusrat, A
机构
[1] Emory Univ, Dept Pathol & Lab Med, Epithelial Pathobiol Res Unit, Atlanta, GA 30322 USA
[2] Univ Munster, Dept Gen Surg, Munster, Germany
关键词
apical junctional complex; Crohn's disease; cytokines; epithelia; inflammatory bowel disease; intestine;
D O I
10.1097/01.mog.0000203864.48255.4f
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Purpose of review Epithelial intercellular junctions are important components of the epithelial barrier and are compromised in disorders such as Crohn's disease. We will highlight recent progress in understanding the role of an intercellular junction referred to as the apical junctional complex in regulating small intestinal epithelial permeability in health and disease. Recent findings Recent studies have implicated aberrant regulation of the AJC as an underlying factor contributing to a leaky epithelial barrier in Crohn's patients. Consequences of increased epithelial permeability include exposure of intestinal tissue to luminal antigens/pathogens which in turn influence disease activity. Furthermore, proinflammatory cytokines released into the milieu of the epithelium in patients with Crohn's disease influence apical junctional complex and epithelial barrier function. Such cytokines induce disassembly of the apical junctional complex by promoting differential endocytosis of component proteins. Additionally, apical junctional complex proteins are targeted by pathogens that use the epithelium as a portal of entry to establish disease in the host. Summary The epithelial apical junctional complex is important in determining epithelial barrier properties. Recent studies have highlighted contribution of proinflammatory cytokines and endocytosis of apical junctional complex proteins to the epithelial barrier defect. Continued advances in understanding of this field will yield new therapeutic targets for intestinal disorders.
引用
收藏
页码:85 / 89
页数:5
相关论文
共 58 条
[1]   Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation [J].
Berkes, J ;
Viswanathan, VK ;
Savkovic, SD ;
Hecht, G .
GUT, 2003, 52 (03) :439-451
[2]  
Breslin NP, 2001, AM J GASTROENTEROL, V96, P2934
[3]  
Brown SJ, 2005, CURR OPIN DRUG DISC, V8, P160
[4]   Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms [J].
Bruewer, M ;
Luegering, A ;
Kucharzik, T ;
Parkos, CA ;
Madara, JL ;
Hopkins, AM ;
Nusrat, A .
JOURNAL OF IMMUNOLOGY, 2003, 171 (11) :6164-6172
[5]   Interferon-γ induces internalization of epithelial tight junction proteins via a macropinocytosis-like process [J].
Bruewer, M ;
Utech, M ;
Ivanov, AI ;
Hopkins, AM ;
Parkos, CA ;
Nusrat, A .
FASEB JOURNAL, 2005, 19 (08) :923-933
[6]  
BUHNER S, 2005, GUT 0729
[7]   Junctional adhesion molecule a serves as a receptor for prototype and field-isolate strains of mammalian reovirus [J].
Campbell, JA ;
Schelling, P ;
Wetzel, JD ;
Johnson, EM ;
Forrest, JC ;
Wilson, GAR ;
Aurrand-Lions, M ;
Imhof, BA ;
Stehle, T ;
Dermody, TS .
JOURNAL OF VIROLOGY, 2005, 79 (13) :7967-7978
[8]   Effect of bile on the cell surface permeability barrier and efflux system of Vibrio cholerae [J].
Chatterjee, A ;
Chaudhuri, S ;
Saha, G ;
Gupta, S ;
Chowdhury, R .
JOURNAL OF BACTERIOLOGY, 2004, 186 (20) :6809-6814
[9]   Interferon γ induces translocation of commensal Escherichia coli across gut epithelial cells via a lipid raft-mediated process [J].
Clark, E ;
Hoare, C ;
Tanianis-Hughes, J ;
Carlson, GL ;
Warhurst, G .
GASTROENTEROLOGY, 2005, 128 (05) :1258-1267
[10]   A porous defense: the leaky epithelial barrier in intestinal disease [J].
Clayburgh, DR ;
Shen, L ;
Turner, JR .
LABORATORY INVESTIGATION, 2004, 84 (03) :282-291