Fusarium Mycotoxins Disrupt the Barrier and Induce IL-6 Release in a Human Placental Epithelium Cell Line

Abstract

Deoxynivalenol, T-2 toxin, and zearalenone, major Fusarium mycotoxins, contaminate human food on a global level. Exposure to these mycotoxins during pregnancy can lead to abnormalities in neonatal development. Therefore, the aim of this study was to investigate the effects of Fusarium mycotoxins on human placental epithelial cells. As an in vitro model of placental barrier, BeWo cells were exposed to different concentrations of deoxynivalenol, zearalenone or T-2 toxin. Cytotoxicity, effects on barrier integrity, paracellular permeability along with mRNA and protein expression and localization of junctional proteins after exposure were evaluated. Induction of proinflammatory responses was determined by measuring cytokine production. Increasing mycotoxin concentrations affect BeWo cell viability, and T-2 toxin was more toxic compared to other mycotoxins. Deoxynivalenol and T-2 toxin caused significant barrier disruption, altered protein and mRNA expression of junctional proteins, and induced irregular cellular distribution. Although the effects of zearalenone on barrier integrity were less prominent, all tested mycotoxins were able to induce inflammation as measured by IL-6 release. Overall, Fusarium mycotoxins disrupt the barrier of BeWo cells by altering the expression and structure of junctional proteins and trigger proinflammatory responses. These changes in placental barrier may disturb the maternal–fetal interaction and adversely affect fetal development.

Zearalenone and the Immune Response

“…In a model monocytic cell line, hER + IL-1β-CAT+, the exposure of the cells to low level 50 ng/mL of zearalenone and α-zearalenol resulted in a pro-inflammatory effect as 17β-estradiol by modulating and promoting IL-1β synthesis. The toxins manifested full agonist activity with 17β-estradiol but at lower potency [ 62 ] exposure of human placental choriocarcinoma (BeWo) cells to different concentrations of ZEA (2–16µM) increased the IL-6 production [ 63 ].…”

Bacillus velezensis A2 Inhibited the Cecal Inflammation Induced by Zearalenone by Regulating Intestinal Flora and Short-Chain Fatty Acids

“…There are many microorganisms in the human intestine: exploring the interaction between microorganisms and their host has research value in evaluating the relationship between microorganisms and intestinal diseases ( 5 ). For example, microbes can prevent pathogens from settling in the gut, protect the intestinal barrier capacity, and regulate the associated lymphoid tissue and immune function in the gut ( 7 ). Use of beneficial microbes to protect animals from colonization and infection by intestinal pathogens is known as ‘colonization resistance,’ which arises from the interaction between intestinal microbes and the mucosal surface, epithelial cells, and immune system ( 8 ).…”

Mycotoxins: Biotransformation and Bioavailability Assessment Using Caco-2 Cell Monolayer

“…The major fungal genera producing foodborne mycotoxins are Fusarium , Aspergillus, Penicillium , and Alternaria [ 4 , 5 ]. Fusarium is one of the most important producers of toxins falling into the three major classes of mycotoxins, such as fumonisins (FBs), zearalenone (ZEA), trichothecenes (deoxynivalenol (DON), nivalenol (NIV), and T-2 and HT-2 toxins, and also emerging mycotoxins involving beauvericin (BEA) and enniatins (ENNs) [ 6 , 7 ]. Ochratoxin A (OTA), the major mycotoxin of the ochratoxins, is produced by various species of the Aspergillus and Penicillium genus [ 8 ].…”