Artículo
Sterile inflammation drives multiple programmed cell death pathways in the gut
Ruera, Carolina Naymé
; Miculán, Emanuel Gonzalo
; Pérez, Federico; Ducca, Gerónimo Marcelo
; Carasi, Paula
; Chirdo, Fernando Gabriel
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Fecha de publicación:
09/2020
Editorial:
Federation of American Societies for Experimental Biology
Revista:
Journal of Leukocyte Biology
ISSN:
0741-5400
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Intestinal epithelial cells have a rapid turnover, being rapidly renewed by newly differentiated enterocytes, balanced by massive and constant removal of damaged cells by programmed cell death (PCD). The main forms of PCD are apoptosis, pyroptosis, and necroptosis, with apoptosis being a noninflammatory process, whereas the others drive innate immune responses. Although apoptosis is thought to be the principal means of cell death in the healthy intestine, which mechanisms are responsible for PCD during inflammation are not fully understood. To address this question, we used an in vivo model of enteropathy in wild-type mice induced by a single intragastric administration of the p31-43 gliadin peptide, which is known to elicit transient MyD88, NLRP3, and caspase-1-dependent mucosal damage and inflammation in the small intestine. Here, we found increased numbers of TUNEL+ cells in the mucosa as early as 2 h after p31-43 administration. Western blot and immunofluorescence analysis showed the presence of caspase-3-mediated apoptosis in the epithelium and lamina propria. In addition, the presence of mature forms of caspase-1, IL-1β, and gasdermin D showed activation of pyroptosis and inhibition of caspase-1 led to decreased enterocyte death in p31-43-treated mice. There was also up-regulation of RIPK3 in crypt epithelium, suggesting that necroptosis was also occurring. Taken together, these results indicate that the inflammatory response induced by p31-43 can drive multiple PCD pathways in the small intestine.
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Articulos(IIFP)
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Citación
Ruera, Carolina Naymé; Miculán, Emanuel Gonzalo; Pérez, Federico ; Ducca, Gerónimo Marcelo; Carasi, Paula; et al.; Sterile inflammation drives multiple programmed cell death pathways in the gut; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 109; 1; 9-2020; 211-221
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