Down-regulation of NF-κB signaling by <i>Gordonia bronchialis</i> prevents the activation of gut epithelial cells

Abstract

The immunomodulatory power of heat-killed <i>Gordonia bronchialis</i> was studied on gut epithelial cells activated with pro-inflammatory stimuli (flagellin, TNF-α or IL-1β). Light emission of luciferase-transfected epithelial cells and mRNA expression of IL-1β, TNF-α, IL-6, CCL20, IL-8 and MCP-1 were measured. NF-κB activation was assessed by immunofluorescence and immunoblotting, and induction of reactive oxygen species (ROS) was evaluated. <i>In vivo</i> inhibitory properties of <i>G. bronchialis</i> were studied with ligated intestinal loop assay and in a mouse model of food allergy. <i>G. bronchialis</i> promoted the down-regulation of the expression of CCL20 and IL-1β on activated epithelial cells in a dose-dependent manner. A concomitant blocking of nuclear p65 translocation with increased production of ROS was found. <i>In vivo</i> experiments confirmed the inhibition of CCL20 expression and the suppression of IgE sensitization and hypersensitivity symptoms in the food allergy mouse model. In conclusion, heat-killed <i>G. bronchialis</i> inhibited the activation of NF-κB pathway in human epithelial cells, and suppressed the expression of CCL20. These results indicate that <i>G. bronchialis</i> may be used to modulate the initial steps of innate immune activation, which further suppress the allergic sensitization. This approach may be exploited as a therapy for intestinal inflammation.