Interleukin-10 enhances the intestinal epithelial barrier in the presence of corticosteroids through p38 MAPK activity in Caco-2 monolayers : a possible mechanism for steroid responsiveness in ulcerative colitis
Lorén Moreno, Violeta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cabré i Gelada, Eduard (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ojanguren, Isabel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Domènech, Eugeni (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pedrosa Tapias, Elisabet (Institut Germans Trias i Pujol)
Garcia-Jaraquemada, Arce (Institut Germans Trias i Pujol)
Mañosa i Ciria, Míriam (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Manyé Almero, Josep (Institut Germans Trias i Pujol)

Fecha:	2015
Resumen:	Glucocorticosteroids are the first line therapy for moderate-severe flare-ups of ulcerative colitis. Despite that, up to 60% of patients do not respond adequately to steroid treatment. Previously, we reported that low IL-10 mRNA levels in intestine are associated with a poor response to glucocorticoids in active Crohn's disease. Here, we test whether IL-10 can favour the response to glucocorticoids by improving the TNFα-induced intestinal barrier damage (assessed by transepithelial electrical resistance) in Caco-2 monolayers, and their possible implications on glucocorticoid responsiveness in active ulcerative colitis. We show that the association of IL-10 and glucocorticoids improves the integrity of TNFα-treated Caco-2 cells and that p38 MAPK plays a key role. In vitro, IL-10 facilitates the nuclear translocation of p38 MAPK-phosphorylated thereby modulating glucocorticoids-receptor-α, IL-10-receptor-α and desmoglein-2 expression. In glucocorticoids-refractory patients, p38 MAPK phosphorylation and membrane desmoglein-2 expression are reduced in colonic epithelial cells. These results suggest that p38 MAPK-mediated synergism between IL-10 and glucocorticoids improves desmosome straightness contributing to the recovery of intestinal epithelium and reducing luminal antigens contact with lamina propria in ulcerative colitis. This study highlights the link between the intestinal epithelium in glucocorticoids-response in ulcerative colitis.
Ayudas:	Ministerio de Educación y Ciencia BFU 2006-15063-C03-2
Nota:	Altres ajuts: 2012 Spanish Gastroenterological Association i CIBER G0034
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Gastrointestinal tract ; Caco-2 cells ; Epithelial cells ; Biopsy ; MAPK signaling cascades ; Ulcerative colitis ; Desmosomes ; Epithelium
Publicado en:	PloS one, Vol. 10, No 6 (June 2015) , p. e0130921, ISSN 1932-6203

DOI: 10.1371/journal.pone.0130921
PMID: 26090671

16 p, 1.8 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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