Article ID Journal Published Year Pages File Type
2601598 Toxicology Letters 2008 10 Pages PDF
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.

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