Biology subjects

Partsch, V.

Publications and source records attributed to Partsch, V..

3 recordsLinked to original sources

bioRxiv2026

From cellular stress to cytokine modulation: An in vitro study of intestinal effects of major Alternaria mycotoxins

Mycotoxins are frequently detected in food, making the gastrointestinal tract the first organ exposed. Here, we used various in vitro intestinal cell models to explore the barrier and immune responses to the Alternaria mycotoxins alternariol (AOH), alternariol methyl ether (AME), altenuene (ALT), altertoxin I (ATX-I), tentoxin (TEN), and tenuazonic acid (TeA). The mycotoxins exhibited low toxicity in undifferentiated Caco-2 cells, but AOH, AME, and ATX-I affected the cell cycle and reactive oxygen species (ROS) levels. None of the toxins alone or in combination with IL-1beta; had any effect on the barrier integrity or viability of the differentiated Caco-2/HT29-MTX-E12 co-culture. Furthermore, AOH and AME reduced IL-1beta-induced IL-8 secretion, whereas TeA increased the secretion, demonstrating immunomodulatory effects. For verification, we used the more in vivo-like EpiIntestinal TM model, which is based on human primary cells. AOH, AME, and TeA had minor effects on viability without compromising barrier integrity; also, cytokine secretion was less affected than in the co-culture model. Studies on uptake confirmed low absorption of AOH, AME, and TeA. Overall, the studies indicate a low absorption and moderate effects of the toxins on the gastrointestinal tract.

cell biology↗

bioRxiv2026

Modulation of NF-κB signaling by Alternaria mycotoxins: in vitro and in silico insights into molecular mechanisms of immunosuppression in THP-1 monocytes

Alternaria fungi produce various structurally diverse mycotoxins, several of which exhibit immunomodulatory properties. Among these, alternariol monomethyl ether (AME), alternariol (AOH), alterperylenol (ALTP), altertoxin I (ATX-I), and altersetin (AST) have been reported to suppress lipopolysaccharide (LPS)-induced inflammatory responses. However, the precise molecular mechanisms underlying these effects remain unclear. The present study aimed to elucidate how these selected Alternaria mycotoxins (0.1-50 {micro}M) target the NF-{kappa}B signaling pathway in THP-1 monocytes. Key components of the NF-{kappa}B cascade were analyzed by immunofluorescence microscopy, Western blotting and qRT-PCR. Nuclear translocation of NF-{kappa}B p65 and its phosphorylated form (p- NF-{kappa}B p65) was assessed by Western blot, while cytokine responses were determined at transcript (qRT-PCR) and protein (ELISA) levels. Moreover, in silico docking analyses were performed to investigate potential interactions of the toxins with IKK{beta}, and receptor-mediated crosstalk was studied using the glucocorticoid receptor (GR) antagonist RU486. Co-treatment with RU486 attenuated the immunosuppressive effects of 1 and 5 {micro}M AOH, indicating partial involvement of GR-dependent mechanisms. AME, AOH, ALTP, ATX-I, and AST increased total I{kappa}B levels while reducing its phosphorylated form. Additionally, AST and ALTP decreased the protein levels of Toll-like receptor 4 (TLR4), the I{kappa}B kinase (IKK) complex, NF-{kappa}B p65, and p- NF-{kappa}B p65. While AOH (5 {micro}M) and AST (25 {micro}M) reduced nuclear translocation of p65 and p-p65, ALTP (2 {micro}M) enhanced nuclear localization despite decreasing cytokine expression Together, these findings suggest toxin-specific interference at multiple regulatory levels of NF-{kappa}B signaling and provide novel mechanistic insight into the immunomodulatory effects of Alternaria mycotoxins.

pharmacology and toxicology↗

bioRxiv2026

Opposing immunomodulatory effects of the Alternaria mycotoxin tenuazonic acid in immune and intestinal epithelial cells

Tenuazonic acid (TeA) is one of the most frequently detected Alternaria mycotoxins in contaminated food. Despite its frequent occurrence, its immunomodulatory effects remain insufficiently characterized. Therefore, the present study investigated the impact of TeA on inflammatory signaling and cytokine regulation in monocytes and intestinal epithelial cell (IEC) models. NF-{kappa}B activity was assessed using a reporter gene assay in THP1-Lucia monocytes, while cytokine mRNA expression and protein secretion were quantified in Caco-2 and HCEC-1CT cells by qRT-PCR and ELISA, respectively. In THP-1 monocytes, TeA significantly suppressed lipopolysaccharide (LPS)-induced NF-{kappa}B activation in a concentration-dependent manner starting at 25 M, while cytotoxicity occurred only at concentrations [≥]100 M. In HCEC-1CT and differentiated Caco-2 cells, TeA increased IL-6, IL-8, and TNF- mRNA levels at non-cytotoxic concentrations ([≥]10 M). In Caco-2 cells, these transcriptional changes were accompanied by increased cytokine secretion, whereas HCEC-1CT cells showed only partial effects on the protein level after short-term exposure. Following prolonged incubation, TNF- secretion was increased and IL-6 and IL-8 secretion were slightly reduced. IL-10 remained unaffected under all conditions. Overall, TeA exerted cell type-dependent immunomodulatory effects characterized by immunoinhibitory activity in monocytes and pro-inflammatory responses in IECs, highlighting the complex immunotoxic potential of this Alternaria mycotoxin.

pharmacology and toxicology↗