Modulatory effect of Actinomycetales genera on activation of gut epithelial cells and inhibition of Nuclear Factor -KB pathway

PAOLA SMALDINI; JOHN L STANFORD; DAVID ROMANIN; CARLOS A. FOSSATI; GUILLERMO H DOCENA

INNATE IMMUNITY

SAGE PUBLICATIONS LTD

Lugar: London; Año: 2013 p. 1 - 13

1753-4259

The immunomodulatory power of heat-killed Gordonia bronchialis was studied on gut epithelial cells activated with pro-inflammatory stimuli (flagellin, TNF-á or IL-1â). Light emission of luciferase transfected epithelial cells and mRNA expression of IL-1â, TNF-á, IL6, CCL20, IL-8 and MCP-1 were measured. NF-êB activation was assessed by immunofluorescence and immunoblotting, and induction of reactive oxygen species was evaluated. In vivo inhibitory properties of Gordonia bronchialis were studied with ligated intestinal loop assay and in a murine model food allergy. Gordonia bronchialis promoted the down-regulation of the expression of CCL20 and IL-1 â on activated epithelial cells in a dose-dependent manner. A concomitant blocking of nuclear p65 traslocation with increased production of reactive oxygen species was found. In vivo experiments confirmed the inhibition of CCL20 expression and the suppression of IgE sensitization and hypersensitivity symptoms in the food allergy mouse model. In conclusion, dead Gordonia bronchialis inhibited the activation of NF-êB pathway in human epithelial cells, and suppressed the expression of CCL20. These results indicate that Gordonia bronchialis may be used to modulate the initial steps of innate immune activation, which further suppress of the allergic sensitization. This approach may be exploited as a therapy for intestinal inflammation.