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Woelflingseder, L; Gruber, N; Adam, G; Marko, D.
(2020): Pro-Inflammatory Effects of NX-3 Toxin Are Comparable to Deoxynivalenol and not Modulated by the Co-Occurring Pro-Oxidant Aurofusarin
MICROORGANISMS. 2020; 8(4), 603 FullText FullText_BOKU

Abstract:: The type A trichothecene NX-3, produced by certain Fusarium graminearum strains, is similar to the mycotoxin deoxynivalenol (DON), with the exception that it lacks the carbonyl moiety at the C-8 position. NX-3 inhibits protein biosynthesis and induces cytotoxicity to a similar extent as DON, but so far, immunomodulatory effects have not been assessed. In the present study, we investigated the impact of NX-3 on the activity of the nuclear factor kappa B (NF-kappa B) signaling pathway in direct comparison to DON. Under pro-inflammatory conditions (IL-1 beta treatment), the impact on cytokine mRNA levels of NF-kappa B downstream genes was studied in human colon cell lines, comparing noncancer (HCEC-1CT) and cancer cells (HT-29). In addition, potential combinatory effects with the co-occurring Fusarium secondary metabolite aurofusarin (AURO), a dimeric naphthoquinone known to induce oxidative stress, were investigated. NX-3 and DON (1 mu M, 20 h) significantly activated a NF-kappa B regulated reporter gene to a similar extent. Both trichothecenes also enhanced transcript levels of the known NF-kappa B-dependent pro-inflammatory cytokines IL-8, IL-6, TNF-alpha and IL-1 beta. Comparing the colon cancer HT-29 and noncancer HCEC-1CT cells, significant differences in cytokine signaling were identified. In contrast, AURO did not affect NF-kappa B pathway activity and respective cytokine expression levels at the tested concentration. Despite its pro-oxidant potency, the combination with AURO did not significantly affect the immunomodulatory effects of the tested trichothecenes. Taken together, the present study reveals comparable potency of DON and NX-3 with respect to immunomodulatory and pro-inflammatory potential. Consequently, not only DON but also NX-3 should be considered as factors contributing to intestinal inflammatory processes.
Authors BOKU Wien:: Adam Gerhard
Find related publications in this database (Keywords): mycotoxin; trichothecene; NF-kappa B; intestinal inflammation; combinatory effects; food safety