Zearalenone inhibits T cell chemotaxis by inhibiting cell adhesion and migration related proteins.

Zearalenone (ZEA) is a phenolic resorcylic acid lactone mycotoxin produced by several Fusarium species that grow on temperate and tropical crops. The number of reports documenting the immunotoxic effects of ZEA is increasing, but the underlying mechanism is not clear. The purpose of this study was to investigate the effects of ZEA on T cell chemotaxis and evaluate changes in adhesion and migration proteins associated with this process. Specifically, T cells were isolated from BALB/C mouse splenic lymphocytes, activated by concanavalin A (Con A), and then exposed to different concentrations of ZEA. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used observe the ultrastructural changes inside the cell and on the cell surface, respectively. The transwell migration assay was used to evaluate the effect of ZEA on T cell chemotaxis in the presence of CCL19 or CCL21. A confocal 3D laser was used to capture the morphology of perforated cells and western blot was used to detect the expression of proteins associated with cell migration and adhesion. Additionally, we used flow cytometry to examine the expression of chemokine receptors on T cells. Finally, the chemokine (RANTES and MIP-1α) levels secreted by T cells were assessed using cytometric bead array. Overall, our data showed that treatment with ZEA caused ultrastructural damage on the surface as well as inside of T cells. Moreover, ZEA inhibited T cell chemotaxis which was mediated by CCL19 or CCL21 and disrupted the balance of T cell subtypes. The expression of T cell adhesion and migration proteins was also inhibited by ZEA. The expression of T cell chemokine receptor as well as secretion of RANTES and MIP-1α by T cells was suppressed after ZEA treatment. In summary, our results indicate that ZEA reduced the chemotactic effect of T cells mediated by chemokines, which was likely linked to the inhibition of T cell motility and accompanied by decreased expression of adhesion and migration proteins.

Zearalenone impairs the male reproductive system functions via inducing structural and functional alterations of sertoli cells.

The aim of this study was to investigate the effects of ZEA on the cytoskeletal structure, and factors specifically expressed by Sertoli cells. Primary Sertoli cells from rats aged 18-21 days were exposed to increasing ZEA concentrations (0, 5, 10, 20 µg mL(-1)) for 24 h. The results of immunofluorescence showed disruption of α-tubulin filaments and F-actin bundles, and damage to the nucleus of Sertoli cells on exposure to ZEA. In the control group, the protein level expression of androgen-binding protein (ABP), transferrin, vimentin, N-cadherin, and follicle-stimulating hormone receptor (FSHR) were decreased significantly (p<0.05, p<0.01). The mRNA levels of ABP, transferrin, vimentin, N-cadherin, and FSHR varied significantly in the experimental group (p<0.05). The results of enzyme-linked immunosorbent assay indicated a significant decrease in the levels of inhibin-ß and transferrin in the cultural supernatants (p<0.05). Additionally, the ultrastructural analysis indicated the absence of mitochondria and Golgi apparatus, and presence of vacuoles in the cytoplasm. These findings showed that ZEA treatment can damage the cytoskeletal structure and affect specific secretory functions of Sertoli cells, which may be an underlying cause of ZEA-induced reproductive toxicity.