Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017536 (giardiasis)
 1,714 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently demonstrated that Giardia lamblia rearranges cytoskeletal proteins and reduces transepithelial electrical resistance. The effect of G. lamblia on enterocyte apoptosis is unknown, and a possible link between microbially induced enterocyte apoptosis and altered epithelial permeability has yet to be established. The aim of this study was to assess whether G. lamblia induces enterocyte apoptosis in duodenal epithelial monolayers and whether this effect increases epithelial permeability. Monolayers of nontransformed human duodenal epithelial cells were incubated with sonicated or live G. lamblia trophozoites (NF, S2, WB, or PB strains) for 8, 24, and 48 h. Cell cultures were assessed for apoptosis by Hoechst fluorescence staining, enzyme-linked immunosorbent assay for apoptotic nucleosomes, and electron microscopy. In separate experiments, monolayers were pretreated with or without 120 microM caspase-3 inhibitor (Z-DEVD-FMK) for 1 h and were assessed for production of apoptotic nucleosomes, tight junctional integrity (with fluorescent ZO-1 staining followed by confocal laser microscopy), and transepithelial permeability for fluorescein isothiocyanate-dextran. G. lamblia strains NF and S2, but not strains WB or PB, induced enterocyte apoptosis within the monolayers, and this effect was inhibited by Z-DEVD-FMK pretreatment. Using the G. lamblia NF isolate, additional experiments investigated the possible link between enterocyte apoptosis and altered epithelial permeability. G. lamblia NF disrupted tight junctional ZO-1 and increased epithelial permeability, but these effects were also prevented by pretreatment with the caspase-3 inhibitor. These findings indicate that strain-dependent induction of enterocyte apoptosis may contribute to the pathogenesis of giardiasis. This effect is responsible for a loss of epithelial barrier function by disrupting tight junctional ZO-1 and increasing permeability in a caspase-3-dependent manner.
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PMID:Strain-dependent induction of enterocyte apoptosis by Giardia lamblia disrupts epithelial barrier function in a caspase-3-dependent manner. 1206 9

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.
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PMID:Giardia lamblia disrupts tight junctional ZO-1 and increases permeability in non-transformed human small intestinal epithelial monolayers: effects of epidermal growth factor. 1216 16