Physio-pathological parameters affect the activation of inflammatory pathways by deoxynivalenol in Caco-2 cells

The intake of deoxynivalenol (DON), a mycotoxin contaminating cereal food items, causes gastro-intestinal illness inhuman and animal. This study investigated whether intracellular inflammatory cascades (MAPKs and NF-kapa B), cell maturity(proliferat in vs. differentiated), cell state(control vs. inflamed) and exposure duration(chronic vs. acute)affect IL-8 secretion and PGE-2synthes is in Caco-2cells exposed to plausible intestinal concentrations (50, 500and5000ng/ml)of DON. IL-8secretionandPGE-2 synthesizing capacity were dose-dependently upregulated in differentiated Caco-2cells exposed to DON during 24h, reaching an increase of Deoxynivalenol Inflammatorycascades Cell differentiation Intestinal inflammation 25 and 1.7-foldrespectively, whereas transcript level of IL-8 and COX-2 were increased by 40 and 17-fold. Similar results were obtained with proliferating cells. The upregulation decreased upon simultaneous incubation with inhibitors of MAPKsERK1/2 or p38 or of transcription factor NF-jB. IL-8 secretion and PGE-2 synthesizing capacity increased respectively by 15 and 2-fold after chronic 21 day incubation with DON (50ng/ml). IL-8 production was exacerbated (510-foldversus negative control)upon simultaneous exposure to inflammatory stimuli. These results suggest activation of inflammatory pathways in intestinal epithelial cells exposed chronically or acutely to DON. The sensitivity to DON, where as not affected by cell differentiation, is exacerbated by the presence of additional stimuli.