AI Article Synopsis

  • * The study investigates the effects of interleukin-10 (IL-10) on improving the response to glucocorticoids by enhancing the intestinal barrier in lab models and identifies key molecular processes involved, including the role of p38 MAPK.
  • * Findings suggest that combining IL-10 with glucocorticoids can better restore the integrity of the intestinal lining, potentially benefiting patients who previously had limited responses to steroid treatments.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474693PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130921PLOS

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