Oxidative stress induced by Se-deficient high-energy diet implicates neutrophil dysfunction via Nrf2 pathway suppression in swine.

Tianshu Yang,Pengzu Wang,Zeping Zhao,Xin Gen Lei,Shiwen Xu,Tianqi Liu,Anshan Shan,Ziwei Zhang

doi:10.18632/oncotarget.14550

Tianshu Yang, Pengzu Wang + Show 6 more

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https://doi.org/10.18632/oncotarget.14550

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Abstract

The mechanism of the interaction between Se deficiency and high energy remains limited. The aim of the current study was to identify whether Se-deficient, high-energy diet can induce oxidative stress, and downregulate the Nrf2 pathway and phagocytic dysfunction of neutrophils. We detected the phagocytic activity, ROS production, protein levels of Nrf2 and Nrf2 downstream target genes, and the mRNA levels of 25 selenoproteins, heat shock proteins, and cytokines in neutrophils. Cytokine ELISA kits were used to measure the serum cytokines. The concentration of ROS was elevated (P < 0.05) in obese swine fed on a low Se diet (less than 0.03 mg/kg Se) compared to control swine. The protein levels of Nrf2 and its downstream target genes were depressed during Se deficiency and high-energy intake. The mRNA levels of 16 selenoproteins were significantly decreased (P < 0.05) in the Se-deficient group and Se-deficient, high-energy group compared to the control group. However, the mRNA levels of 13 selenoproteins in peripheral blood neutrophils were upregulated in high energy group, except TrxR1, SelI and SepW. In summary, these data indicated that a Se-deficient, high-energy diet inhibits the Nrf2 pathway and its regulation of oxidative stress, and prompted a pleiotropic mechanism that suppresses phagocytosis.

Highlights

The nutrient elements of animal diets are key to redox homeostasis and the functions of the body’s immune system
To further link reactive oxygen species (ROS) generation to neutrophil phagocytosis, we evaluated the level of nuclear factor E2-related factor 2 (Nrf2), the downstream genes, 25 selenoproteins, heat shock proteins (HSPs) and relevant cytokines, which were acquired from swine fed with a Se-deficient, high-energy diet
To confirm whether Se deficiency and high-energy diets affect the function of neutrophils, swine neutrophils were freshly isolated from a control group, Se– group, energy+ group, and Se–-energy+ group

Summary

Introduction

The nutrient elements of animal diets are key to redox homeostasis and the functions of the body’s immune system. Several studies reported that Se deficiency disrupted the expression of selenoproteins in many tissues and organs of livestock and humans [4, 5] In these situations, immune system dysfunction is caused by oxidative stress and the generation of ROS. High-energy diet results in obesity, the continuous generation of ROS from the stimulation of a metabolic surplus, and a drop in the immune function of the body by remaining in a persistent condition of oxidative stress This induces low-grade, chronic inflammation from the generation of lipid peroxidation and enhances the expression quantity of pro-inflammatory cytokines, such as IL-1, IL-6, IL-10, TNF-α, and COX-2 [7, 8]

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