Epithelial cell extrusion leads to breaches in the intestinal epithelium.
Inflamm Bowel Dis
; 19(5): 912-21, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23511029
ABSTRACT
BACKGROUND:
Two distinct forms of intestinal epithelial cell (IEC) extrusion are described 1 with preserved epithelial integrity and 1 that introduced breaches in the epithelial lining. In this study, we sought to determine the mechanism underlying the IEC extrusion that alters the permeability of the gut epithelium.METHODS:
IEC extrusions in polarized T84 monolayer were induced with nigericin. Epithelial permeability was assessed with transepithelial electrical resistance and movements of latex microspheres and green fluorescent protein-transfected Escherichia coli across the monolayer. In vivo IEC extrusion was modulated in wild-type and a colitic (interleukin-10 knock-out) mouse model with caspase-1 activation and inhibition. Luminal aspirates and mucosal biopsies from control patients and patients with inflammatory bowel disease were analyzed for caspase-1 and caspase-3&7 activation.RESULTS:
Caspase-1-induced IEC extrusion in T84 monolayers resulted in dose-dependent and time-dependent barrier dysfunction, reversible with caspase-1 inhibition. Moreover, the movements of microspheres and microbes across the treated epithelial monolayers were observed. Increased caspase-1-mediated IEC extrusion in interleukin-10 knock-out mice corresponded to enhanced permeation of dextran, microspheres, and translocation of E. coli compared with wild type. Caspase-1 inhibition in interleukin-10 knock-out mice resulted in a time-dependent reduction in cell extrusion and normalization of permeability to microspheres. Increased IEC extrusion in wild-type mice was induced with caspase-1 activation. In human luminal aspirates, the ratio of positively stained caspase-1 to caspase-3&7 cells were 11 and 21 in control patients and patients with inflammatory bowel disease, respectively; these observations were confirmed by cytochemical analysis of mucosal biopsies.CONCLUSIONS:
IEC extrusion mediated by caspase-1 activation contributes to altered intestinal permeability in vitro and in vivo.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Inflamatorias del Intestino
/
Permeabilidad de la Membrana Celular
/
Interleucina-10
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Extensiones de la Superficie Celular
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Células Epiteliales
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Mucosa Intestinal
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Idioma:
En
Revista:
Inflamm Bowel Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2013
Tipo del documento:
Article