The Alternaria Mycotoxin Alternariol Triggers the Immune Response of IL‐1β‐stimulated, Differentiated Caco‐2 Cells

Abstract

ScopeAlternariol (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 resultsThe impact of AOH (0.02–40 µm) on inflammatory signaling in either IL‐1β‐stimulated or non‐stimulated differentiated Caco‐2 cells is determined. AOH significantly reduces IL‐1β transcription after 5 h but shows an increasing tendency on IL‐8 transcript levels after long‐term exposure (20 h). In IL‐1β‐stimulated cells, AOH (20–40 µm) augments TNF‐α transcripts while repressing IL‐8, IL‐6, and IL‐1β 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.ConclusionThe obtained data indicate that AOH represses immune responses in an inflamed environment, possibly leading to higher susceptibility to diseases.

Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses

“…An aqueous extract with a low molecular weight (< 3 kDa) fraction of the white button mushroom (Agaricus bisporus) has displayed a responsible activity to the indictors of HCV replication [88]. Alternaroil and alternariol derivatives (alternariol-9-methyl ether-3-O-sulphate and alternariol-9-methyl ether) of an endophytic fungus, Alternaria alternate, and their metabolites were explored for the inhibition of HCV NS3-NS4A protease [89][90][91][92]. Hawas et al [93] found that the most potent HCV NS3/4A protease isolated compound that was obtained from Fusarium equiseti were ω-hydroxyemodin and Griseoxanthone C. Furthermore, mellein, patulin, and H1-A were isolated from Aspergillus ochraceus, Penicillium griseofulvum, and Fusarium oxysporum, respectively.…”

Exposure to Mycotoxin-Mixtures via Breast Milk: An Ultra-Sensitive LC-MS/MS Biomonitoring Approach

“…However, AOH and AME are known for their genotoxic effects in vitro by acting as topoisomerase I or II poison (Jarolim et al 2017). Furthermore, recent studies indicate endocrine disruptive and immune modulatory properties (Dellafiora et al 2018;Kollarova et al 2018;Schmutz et al 2019). Several reports are available on the occurrence of mycotoxins in breast milk and were reviewed before by Warth et al (2016) and Sengling Cebin Coppa et al (2019).…”

Combinatory effects of cereulide and deoxynivalenol on in vitro cell viability and inflammation of human Caco-2 cells

“…A possible reason for the apparent discrepancy might arise from technical issues, namely the fixation of the cells in the SRB assay by trichloroacetic acid (Skehan et al 1990). Caco-2 cells have been reported to possess rigid tight junctions leading to high TEER values of above 400 Ω × cm 2 (Schmutz et al 2019). Therefore, dead cells that are still integrated in the monolayer might be measured as an artefact in total protein content.…”

“…Cells were cultivated under humidified conditions (37 °C, 5% CO 2 , 95% humidity) in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% (v/v) fetal calf serum (FCS), 1% (v/v) penicillin/streptomycin (P/S; 100 U/mL/100 µg/mL), 1% (v/v) potassium pyruvate and 0.01 mg/mL transferrin. Cells were sub-cultivated twice a week at a confluency of 80%, seeded for experiments in 96-well or 24-well tissue culture plates (Cell+, Sarstedt, Nümbrecht, Germany) at a density of 85,000 cells/cm 2 and allowed to grow for 7 days prior to experiments to receive a partially differentiated, tight monolayer as previously reported by Schmutz et al (2019). The used passage numbers were below 40.…”