Modulation of Porcine β-Defensins 1 and 2 upon Individual and Combined Fusarium Toxin Exposure in a Swine Jejunal Epithelial Cell Line

Abstract

dDefensins are small antimicrobial peptides (AMPs) that play an important role in the innate immune system of mammals. Since the effect of mycotoxin contamination of food and feed on the secretion of intestinal AMPs is poorly understood, the aim of this study was to elucidate the individual and combined effects of four common Fusarium toxins, deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEA), and fumonisin B1 (FB1), on the mRNA expression, protein secretion, and corresponding antimicrobial effects of porcine ␤-defensins 1 and 2 (pBD-1 and pBD-2) using a porcine jejunal epithelial cell line, IPEC-J2. In general, upregulation of pBD-1 and pBD-2 mRNA expression occurred following exposure to Fusarium toxins, individually and in mixtures (P < 0.05). However, no significant increase in secreted pBD-1 and pBD-2 protein levels was observed, as measured by enzyme-linked immunosorbent assay (ELISA). Supernatants from IPEC-J2 cells exposed to toxins, singly or in combination, however, possessed significantly less antimicrobial activity against Escherichia coli than untreated supernatants. When single toxins and two-toxin combinations were assessed, toxicity effects were shown to be nonadditive (including synergism, potentiation, and antagonism), suggesting interactive toxin effects when cells are exposed to mycotoxin combinations. The results show that Fusarium toxins, individually and in mixtures, activate distinct antimicrobial defense mechanisms possessing the potential to alter the intestinal microbiota through diminished antimicrobial effects. Moreover, by evaluating toxin mixtures, this improved understanding of toxin effects will enable more effective risk assessments for common mycotoxin combinations observed in contaminated food and feed.

From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol

“…Thus, DON (1 to 20 µM) affects the expression of proteins involved in the epithelial innate immunity, including COX-2 and β-defensins [113,114,115]. Similarly, numerous studies using animal and human cells have demonstrated that DON stimulates the expression and secretion of interleukin-8 (IL-8), a chemoattractant cytokine causing the recruitment/activation of circulating immune cells and thus potentially participating indirectly in the central effects of DON in terms of feed refusal and emesis.…”

Appropriateness to set a group health based guidance value for nivalenol and its modified forms

“…New data on in vitro toxicity of NIV published since the last evaluation (EFSA CONTAM Panel, ) confirm previously known effects such as induction of apoptosis, cytotoxicity, increased secretion of anti‐haematopoietic macrophage inflammatory proteins, reduction of mitochondrial activity and reduced cell proliferation (Wan et al., ,b,c; Nagashima and Nakagawa, ; Park et al., ; Cheat et al., ; Del Regno et al., ; Vejdovszky et al., ).…”

Assessment of urinary biomarkers of mycotoxin exposure in adults from Cameroon

“…One urine sample contained only one mycotoxin, while 20 combinations of two or up to seven mycotoxin urinary biomarkers were observed; more than 70% of the urines contained ve or more different mycotoxins. Complex mixture toxicology remains poorly examined though several groups have recently examined combined effects in vitro [47,48,49,50,51,52,53,54,55,56,57,44,45], with animal studies being more limited [58,59]. These studies remain hard to interpret for public health decisions, but some suggest more than additive effects, thus the mixtures reported here and elsewhere highlight signi cant knowledge gaps.…”