Nrf2-ARE Signaling Partially Attenuates Lipopolysaccharide-Induced Mammary Lesions via Regulation of Oxidative and Organelle Stresses but Not Inflammatory Response in Mice.

Pengfei Hou,Hongyun Liu,Juanjuan Shao,Feng-Qi Zhao,Yongxin Li

doi:10.1155/2021/8821833

Pengfei Hou, Hongyun Liu + Show 3 more

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https://doi.org/10.1155/2021/8821833

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Abstract

The incidence of mastitis is high during the postpartum stage, which causes severe pain and hinders breast feeding in humans and reduces milk production in dairy cows. Studies suggested that inflammation in multiple organs is associated with oxidative stress and nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element pathway is one of the most important antioxidant pathways, but the effects of Nrf2 on antioxidation in the mammary gland during mastitis are still unclear. In this study, intramammary lipopolysaccharide (LPS) challenge was carried out in wild-type (WT) and Nrf2 knockout mice. Results showed that the expression of Nrf2 affected the expression of milk protein genes (Csn2 and Csn3). Importantly, LPS treatment increased the expression of Nrf2 and HO-1 and the content of glutathione in the mammary gland of WT mice, but not in Nrf2(-/-) mice. The expression levels of glutathione synthesis genes (GCLC, GCLM, and xCT) were lower in Nrf2(-/-) mice than in WT mice. Moreover, mitochondrial-dependent apoptotic and endoplasmic reticulum stress were significantly relieved in WT mice compared with that in Nrf2(-/-) mice. In summary, the expression of Nrf2 may play an important role in prevention of oxidative and organelle stresses during endotoxin-induced mastitis in mouse mammary gland.

Highlights

Milk is important for the growth and development of the youth and nutrition of humans
Studies have shown that injury in several organs are closely related to oxidative stress and inflammation, such as kidney injury and liver injury [3, 4], and the production of reactive oxygen species is considered central to the progression of some inflammatory diseases [5]
LPS treatment significantly increased the expression of Csn2 in nuclear factor E2-related factor 2 (Nrf2)(-/-) mice but had no effect on the expression of Csn1s1 and Casein alpha s2 Csn2 (Csn1s2) in all groups (Figures 1(e)–1(g))

Summary

Introduction

Milk is important for the growth and development of the youth and nutrition of humans. The incidence of mastitis arises during lactation, which causes severe pain and even sepsis and hinders breast feeding in humans and reduces milk production in dairy cows [1, 2]. The mammary gland is highly sensitive to LPS, and LPS-induced model is a valuable tool to study the coliform mastitis [2]. Studies have shown that injury in several organs are closely related to oxidative stress and inflammation, such as kidney injury and liver injury [3, 4], and the production of reactive oxygen species is considered central to the progression of some inflammatory diseases [5].

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