The Alternaria Mycotoxin Alternariol Triggers the Immune Response of IL-1ß-stimulated, Differentiated Caco-2 Cells.

ABSTRACT

SCOPE Alternariol (AOH), a toxic secondary metabolite of Alternaria spp., may contaminate a broad spectrum of food and feed. Besides its cytotoxic, genotoxic, and estrogenic properties, several studies report the potential of AOH to suppress the rich network of immune responses. The specific effect of AOH on inflammation-related signaling in non-immune cells of the intestinal epithelial layer has, however, not been investigated yet. Since intestinal epithelial cells (IECs) are, compared to underlying cells, exposed to higher concentrations of the ingested mycotoxin, the question is addressed whether immunomodulation by AOH at the gastrointestinal barrier must be considered. METHODS AND RESULTS: The impact of AOH (0.02-40 µm) on inflammatory signaling in either IL-1ß-stimulated or non-stimulated differentiated Caco-2 cells is determined. AOH significantly reduces IL-1ß transcription after 5 h but shows an increasing tendency on IL-8 transcript levels after long-term exposure (20 h). In IL-1ß-stimulated cells, AOH (20-40 µm) augments TNF-α transcripts while repressing IL-8, IL-6, and IL-1ß transcription as well as IL-8 secretion. Furthermore, inflammation-related microRNAs miR-16, miR-146a, miR-125b, and miR-155 are altered in response to AOH. CONCLUSION: The obtained data indicate that AOH represses immune responses in an inflamed environment, possibly leading to higher susceptibility to diseases.