4-Phenylbutyric acid alleviates 3-acetyldeoxynivalenol-induced immune cells response by inhibiting endoplasmic reticulum stress in mouse spleen

Abstract

3-Acetyldeoxynivalenol (3-Ac-DON), an acetylated derivative of deoxynivalenol (DON), is contaminated grains and grain-based products in general and been harmful to human and animal health. However, the damage effects and regulatory mechanisms to the host immune system have not been well explored. In the present study, our results revealed that 3-Ac-DON significantly decreased spleen index, elevated MPO activity, upregulated mRNA and protein levels of IL-1α, IL-1β, IL-6, IL-17A, TNF-α, M-CSF, G-CSF, CCL2, IFN-β, and IL-10 in the spleen and serum. Interestingly, 4-phenylbutyric acid (4-PBA), an inhibitor of endoplasmic reticulum (ER) stress, largely abolished the above adverse effects. Importantly, 3-Ac-DON enhanced the mRNA abundances of ER stress-related indicators, such as BIP, IRE1A, ATF6, XBP-1, EIF2A, ATF4, and CHOP, which were abolished by 4-PBA, indicating the inhibiting effects of ER stress by 4-PBA in the spleen. Furthermore, 3-Ac-DON reshaped the populations of innate immune cells (neutrophils, macrophages, dendritic cells, natural killer cells) and adaptive immune cells (T lymphocytes, helper T cells, suppressor T cells, and B lymphocytes) in the peripheral blood and spleen lymphocytes. In conclusion, our studies demonstrated that the adverse effects of 3-Ac-DON on immune cells response could be implemented by ER stress and the ameliorative effect of 4-PBA.

Keywords: 3-Acetyldeoxynivalenol; 4-Phenylbutyric acid; ER stress; Immune cell response; Spleen.