| Abstrakt: |
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillusand Penicillium, contaminating in a wide variety of foods and feeds. Mycotoxins, including OTA, could cause immunosuppression in almost all previous studies in vivo. However, the vast majority of results in vitroshowed that mycotoxins caused immunostimulation. Why the results of studies in vitroare contrary to studies in vivois unknown. Our study aims to explore the underlying reason and mechanism of the paradoxical effect. In this study, porcine alveolar macrophage cell line 3D4/21 was chosen as an in vitromodel and treated with 1.0 μg/mL OTA for different times. Some indexes, such as expression of inflammatory cytokines, migration, phagocytosis, macrophage polarization, autophagy-related proteins, and Akt1 phosphorylation, were detected. The results showed that pro-inflammatory cytokine expression, migration, and phagocytosis were increased, with macrophage polarization to the M1 phenotype at 24 h of OTA exposure. Surprisedly, anti-inflammatory cytokine expression was increased, cell phagocytosis and migration were decreased, and macrophage polarization was switched from M1 to M2 at 72 h of OTA exposure. Furthermore, we found that long-time exposure of OTA also suppressed autophagy, and the autophagy activator blocked the OTA-induced immunosuppression. Phosphorylation of Akt1 plays a positive role in autophagy inhibition. In conclusion, long-time instead of short-time exposure of OTA in vitroinduced immunosuppression. The immunosuppression mechanism of OTA in vitroinvolved inhibition of autophagy through upregulating p-Akt1. Our results provide new insight into research on the mechanism of mycotoxin-induced immunosuppression in vitro. |
