title: Cell junction remodeling in gingival tissue exposed to a microbial toxin.
abstract: The gingival epithelium plays a key role in protecting the supporting structures of the teeth from bacteria and their products. In ex vivo experiments, we recently showed that the cytolethal distending toxin (Cdt) from the periodontal pathogen Aggregatibacter actinomycetemcomitans causes extensive damage to gingival tissue. Morphological changes included detachment of the keratinized outer layer, distention of spinous and basal cells in the oral epithelium, disruption of rete pegs, and apparent dissolution of cell junctions. Adherens junctions (zonula adherens) are essential for maintaining barrier function and integrity of gingival epithelium. Therefore, immunohistochemical and RT-PCR analyses of human gingival explants (HGX) and human gingival epithelial cells (HGEC) were utilized for a closer examination of the effects of the Cdt on E-cadherin, the key membrane component of adherens junctions. Although there was some variability among tissue donors, exposure of gingival tissue or isolated epithelial cells to the toxin generally resulted in a pronounced increase in the expression and cytosolic distribution of E-cadherin, accompanied by an increase in levels of the intracellular scaffolding proteins β-catenin and β-actin. These results indicate that the Cdt induced substantial remodeling of adherens junctions, with a potential impact on the barrier function of gingival epithelium.
  
  
  BACKGROUND
  cytolethal distending toxin (Cdt), 4',6-diamidino-2-phenylindole (DAPI), human gingival epithelial cells (HGEC), human gingival explants (HGX), human gingival fibroblasts (HGF), transepithelial resistance (TER).
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: M
authors.initials: M
authors.lastname: Damek-Poprawa
authors.forename: J
authors.initials: J
authors.lastname: Korostoff
authors.forename: R
authors.initials: R
authors.lastname: Gill
authors.forename: J M
authors.initials: JM
authors.lastname: DiRienzo
mesh_terms: D000199:Actins / Q000032:analysis / Q000187:drug effects; D022005:Adherens Junctions / Q000187:drug effects; D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans; D001427:Bacterial Toxins / Q000009:adverse effects*; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D015820:Cadherins / Q000032:analysis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D062445:Claudin-1 / Q000032:analysis / Q000187:drug effects; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005881:Gingiva / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects*; D015603:Keratinocytes / Q000187:drug effects / Q000648:ultrastructure; D010510:Periodontal Diseases / Q000473:pathology; D021122:Protein Subunits / Q000009:adverse effects*; D019108:Tight Junctions / Q000187:drug effects; D013997:Time Factors; D046509:Tissue Culture Techniques; D051176:beta Catenin / Q000032:analysis / Q000187:drug effects
chemical_list: D000199:Actins; D001427:Bacterial Toxins; C568108:CLDN1 protein, human; D015820:Cadherins; D062445:Claudin-1; D021122:Protein Subunits; D051176:beta Catenin; C447141:cytolethal distending toxin, Actinobacillus actinomycetemcomitans
keywords: Aggregatibacter actinomycetemcomitans; E-cadherin; adherens junctions; cytolethal distending toxin; gingival epithelial cells; gingival explants