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Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins.
Am J Pathol. 2001 Dec; 159(6):2001-9.AJ

Abstract

Inflammatory bowel disease (IBD) consisting of ulcerative colitis (UC) and Crohn's (CD) typically displays a waxing and waning course punctuated by disease flares that are characterized by transepithelial migration of neutrophils (PMN) and altered barrier function. Since epithelial barrier function is primarily regulated by the apical most intercellular junction referred to as the tight junction (TJ), our aim was to examine expression of TJ and adherens junction (AJ) proteins in relation to PMN infiltration in mucosal tissue samples from patients with active IBD. Expression of epithelial intercellular TJ proteins (occludin, ZO-1, claudin-1, and JAM) and subjacent AJ (beta-catenin and E-cadherin) proteins were examined by immunoflourescence/confocal microscopy, immunohistochemistry, and Western blotting. Colonic mucosa from patients with UC revealed dramatic, global down-regulation of the key TJ transmembrane protein occludin in regions of actively transmigrating PMN and in quiescent areas in the biopsy samples. Significant decreases in occludin expression were observed at the protein and mRNA levels by Western and Northern blotting. In contrast, expression of other TJ and AJ proteins such as ZO-1, claudin-1, JAM, beta-catenin, and E-cadherin were down-regulated only in epithelial cells immediately adjacent to transmigrating PMN. Analysis of inflamed mucosa from Crohn's disease patients mirrored the results obtained with UC patients. No change in TJ and AJ protein expression was observed in colonic epithelium from patients with collagenous colitis or lymphocytic colitis that are respectively characterized by a thickened subepithelial collagen plate and increased intraepithelial lymphocytes. These results suggest that occludin expression is diminished in IBD by mechanisms distinct from those regulating expression of other intercellular junction proteins. We speculate that down-regulation of epithelial occludin may play a role in enhanced paracellular permeability and PMN transmigration that is observed in active inflammatory bowel disease.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11733350

Citation

Kucharzik, T, et al. "Neutrophil Transmigration in Inflammatory Bowel Disease Is Associated With Differential Expression of Epithelial Intercellular Junction Proteins." The American Journal of Pathology, vol. 159, no. 6, 2001, pp. 2001-9.
Kucharzik T, Walsh SV, Chen J, et al. Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am J Pathol. 2001;159(6):2001-9.
Kucharzik, T., Walsh, S. V., Chen, J., Parkos, C. A., & Nusrat, A. (2001). Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. The American Journal of Pathology, 159(6), 2001-9.
Kucharzik T, et al. Neutrophil Transmigration in Inflammatory Bowel Disease Is Associated With Differential Expression of Epithelial Intercellular Junction Proteins. Am J Pathol. 2001;159(6):2001-9. PubMed PMID: 11733350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. AU - Kucharzik,T, AU - Walsh,S V, AU - Chen,J, AU - Parkos,C A, AU - Nusrat,A, PY - 2001/12/6/pubmed PY - 2002/1/5/medline PY - 2001/12/6/entrez SP - 2001 EP - 9 JF - The American journal of pathology JO - Am J Pathol VL - 159 IS - 6 N2 - Inflammatory bowel disease (IBD) consisting of ulcerative colitis (UC) and Crohn's (CD) typically displays a waxing and waning course punctuated by disease flares that are characterized by transepithelial migration of neutrophils (PMN) and altered barrier function. Since epithelial barrier function is primarily regulated by the apical most intercellular junction referred to as the tight junction (TJ), our aim was to examine expression of TJ and adherens junction (AJ) proteins in relation to PMN infiltration in mucosal tissue samples from patients with active IBD. Expression of epithelial intercellular TJ proteins (occludin, ZO-1, claudin-1, and JAM) and subjacent AJ (beta-catenin and E-cadherin) proteins were examined by immunoflourescence/confocal microscopy, immunohistochemistry, and Western blotting. Colonic mucosa from patients with UC revealed dramatic, global down-regulation of the key TJ transmembrane protein occludin in regions of actively transmigrating PMN and in quiescent areas in the biopsy samples. Significant decreases in occludin expression were observed at the protein and mRNA levels by Western and Northern blotting. In contrast, expression of other TJ and AJ proteins such as ZO-1, claudin-1, JAM, beta-catenin, and E-cadherin were down-regulated only in epithelial cells immediately adjacent to transmigrating PMN. Analysis of inflamed mucosa from Crohn's disease patients mirrored the results obtained with UC patients. No change in TJ and AJ protein expression was observed in colonic epithelium from patients with collagenous colitis or lymphocytic colitis that are respectively characterized by a thickened subepithelial collagen plate and increased intraepithelial lymphocytes. These results suggest that occludin expression is diminished in IBD by mechanisms distinct from those regulating expression of other intercellular junction proteins. We speculate that down-regulation of epithelial occludin may play a role in enhanced paracellular permeability and PMN transmigration that is observed in active inflammatory bowel disease. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/11733350/Neutrophil_transmigration_in_inflammatory_bowel_disease_is_associated_with_differential_expression_of_epithelial_intercellular_junction_proteins_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)63051-9 DB - PRIME DP - Unbound Medicine ER -