Long-time Instead of Short-time Exposure in vitro and Administration in vivo of OTA is Consistent in Immunosuppression.

Long-time Instead of Short-time Exposure in vitro and Administration in vivo of OTA is Consistent in Immunosuppression.

J Agric Food Chem. 2019 Jun 10;:

Authors: Su J, Liu D, Wang Q, Lin J, Song S, Huang K

Abstract
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium, contaminating in a wide variety of food and feeds. Mycotoxins including OTA could cause immunosuppression in almost all previous studies in vivo. However, the vast majority of results in vitro showed that mycotoxins caused immunostimulation. Why the results of studies in vitro are contrary to studies in vivo is unknown. Our study aims to explore the underlying reason and mechanism of the paradoxical effect. In this study, porcine alveolar macrophages (PAMs) cell line 3D4/21 was chosen as an in vitro model and treated with 1.0 μg/mL OTA for different time. Some indexes as expression of inflammatory cytokines, migration, phagocytosis, macrophage polarization, autophagy-related proteins and Akt1 phosphorylation were detected. The results showed that pro-inflammatory cytokines expression, migration and phagocytosis was increased, and macrophage polarization to M1 phenotype at 24 h of OTA exposure. Surprisedly, anti-inflammatory cytokines 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 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 vitro induced immunosuppression. The immunosuppression mechanism of OTA in vitro involving inhibition of autophagy through up-regulating p-Akt1. Our Results provide a new insight into research on mechanism of mycotoxins-induced immunosuppression in vitro.

PMID: 31180669 [PubMed – as supplied by publisher]

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