Deoxynivalenol induces endoplasmic reticulum stress-associated apoptosis via the IRE1/JNK/CHOP pathway in porcine alveolar macrophage 3D4/ 21 cells

The interplay between cell apoptosis and endoplasmic reticulum (ER) stress has garnered increasing attention. Nevertheless, the precise involvement of the unfolded protein response (UPR) signaling in the apoptosis of porcine macrophage cells induced by Deoxynivalenol (DON) remains enigmatic. In this study, we revealed that exposure to 2 mu M DON resulted in a substantial decline in cell viability, concomitant with the initiation of cell apoptosis and the halting of the G1 phase cell cycle in the porcine alveolar macrophage line 3D4/21. Transcriptomic analysis of DON-exposed cells showed distinct expression patterns in 3104 genes, with notable upregulation of ER stress-related genes, including IRE1, CHOP, XBP1 and JNK. Our subsequent validation via qPCR and Western blot analyses confirmed the attenuation of GRP78 and BCL-2, coupled with the upregulation of IRE1, CHOP, JNK, p-JNK, and Bax in DON-induced cells, indicating the instigation of ER stress-associated apoptosis by DON. The addition of 5 mM 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, decreased levels of CHOP, IRE1, JNK, p-JNK, and Bax, while increasing levels of GRP78 and Bcl-2, suggesting that 4-PBA alleviated DON-induced ER stress and apoptosis. Overall, our findings provide new insights into DON-induced ER stress via the IRE1/JNK/CHOP pathway, leading to subsequent cellular apoptosis.

Automated summary

This study reveals the involvement of endoplasmic reticulum (ER) stress in porcine macrophage cell apoptosis induced by Deoxynivalenol (DON). DON exposure leads to upregulation of ER stress-related genes and activates the IRE1/JNK/CHOP pathway, resulting in cellular apoptosis. The ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviates DON-induced ER stress and apoptosis.