Influence of deoxynivalenol on NF-κB activation and IL-8 secretion in human intestinal Caco-2 cells

Abstract

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. In human intestinal Caco-2 cells, DON activates the mitogen-activated protein kinases (MAPKs). We hypothesized a link between DON ingestion and intestinal inflammation, and used Caco-2 cells to assess the effects of DON, at plausible intestinal concentrations (250–10,000 ng/ml), on inflammatory mediators acting downstream the MAPKs cascade i.e. activation of nuclear factor-κB (NF-κB) and interleukin-8 (IL-8) secretion. In addition, Caco-2 cells were co-exposed to pro-inflammatory stimuli in order to mimic an inflamed intestinal epithelium. Dose-dependent increases in NF-κB activity and IL-8 secretion were observed, reaching 1.4- and 7.6-fold, respectively using DON at 10 μg/ml. Phosphorylation of inhibitor-κB (IκB) increased (1.6-fold) at DON levels <0.5 μg/ml. Exposure of Caco-2 cells to pro-inflammatory agents, i.e. 25 ng/ml interleukin-1β, 100 ng/ml tumor necrosis factor-α or 10 μg/ml lipopolysaccharides, activated NF-κB and increased IL-8 secretion. Synergistic interactions between these stimuli and DON were observed. These data show that DON induces NF-κB activation and IL-8 secretion dose-dependently in Caco-2 cells, and this effect was accentuated upon pro-inflammatory stimulation, suggesting DON exposure could cause or exacerbate intestinal inflammation.