Giardia lamblia disrupts tight junctional ZO-1 and increases permeability in non-transformed human small intestinal epithelial monolayers: effects of epidermal growth factor.
In order to improve our understanding of the host cell-parasite interactions in giardiasis, this study assessed the effects of Giardia lamblia on epithelial permeability and tight junctional ZO-1, determined whether epidermal growth factor (EGF) may affect Giardia-induced epithelial injury, and evaluated if EGF modulates epithelial colonization by live G. lamblia trophozoites. Permeability was assessed in assays of trans-epithelial fluxes of FITC-dextran, and ZO-1 integrity was characterized by confocal laser immunofluorescence microscopy in confluent epithelial cell monolayers. G. lamblia significantly increased paracellular permeability and disrupted tight-junctional ZO-1 of a novel non-transformed human small intestinal epithelial cell line (SCBN). Pre-treatment with EGF prevented the development of these abnormalities and significantly inhibited attachment of live trophozoites to the enterocytes, independently of a direct microbiocidal action. These findings demonstrate that G. lamblia may cause intestinal pathophysiology by disrupting tight junctional ZO-1 and increasing epithelial permeability. Apical administration of EGF prevents these abnormalities, and reduces epithelial colonization by the live parasites.
Buret
A G
AG
Department of Biological Sciences, Mucosal Inflammation Research Group, The University of Calgary, Alberta, Canada. aburet@ucalgary.ca
Mitchell
K
K
Muench
D G
DG
Scott
K G E
KG
D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D016829:Giardia lamblia / Q000254:growth & development* / Q000378:metabolism; D005873:Giardiasis / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D006790:Host-Parasite Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D010750:Phosphoproteins / Q000378:metabolism*; D019108:Tight Junctions / Q000502:physiology*; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D004815:Epidermal Growth Factor