Sodium Butyrate Alleviates Lipopolysaccharide-Induced Inflammatory Responses by Down-Regulation of NF-κB, NLRP3 Signaling Pathway, and Activating Histone Acetylation in Bovine Macrophages.

Liqiang Jiang,Aimin Jiang,Di Wu,Xingyi Zhu,Yong Zhang,Ziyi Liu,Zhengkai Wei,Shuangqiu Li,Ershun Zhou,Jingjing Wang,Zhengtao Yang

doi:10.3389/fvets.2020.579674

Liqiang Jiang, Aimin Jiang + Show 9 more

Open Access

https://doi.org/10.3389/fvets.2020.579674

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Abstract

Sodium butyrate is the sodium salt of butyric acid, which possesses many biological functions including immune system regulation, anti-oxidant and anti-inflammatory ability. The present study was designed to elucidate the anti-inflammatory effects and mechanisms of sodium butyrate on lipopolysaccharide (LPS)-stimulated bovine macrophages. The effect of sodium butyrate on the cell viability of bovine macrophages was assayed by using the CCK-8 kit. Quantitative real-time PCR (qRT-PCR) was used to detect the gene expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and inducible Nitric Oxide Synthase (iNOS). NF-κB, NLRP3 signaling pathway, and histone deacetylase were detected by western blotting. The results showed that sodium butyrate had no significant effect on cell viability at 0–1 mM, and inhibited LPS-induced IL-6, IL-1β, COX-2, and iNOS expression. Moreover, sodium butyrate suppressed LPS (5 μg/ml)-stimulated the phosphorylation of IκB and p65, inhibited the deacetylation of histone H3K9, and has also been found to inhibit protein expression in NLRP3 inflammasomes. Thus, our finding suggested that sodium butyrate relieved LPS-induced inflammatory responses in bovine macrophage by inhibiting the canonical NF-κB, NLRP3 signaling pathway, and histone decetylation, which might be helpful to prevent cow mastitis.

Highlights

Bovine mastitis is one of the most common diseases in dairy farming, which causes great economic losses to the world dairy industry [1]
Compared to that of LPS group, mRNA expression of these two enzymes were significantly reduced by sodium butyrate pretreatment (Figure 2), indicating that sodium butyrate possibly suppresses the development of inflammation in bovine macrophages
When the pathogenic microorganisms are not cleared in time, macrophages will release a variety of cytokines to aggravate the inflammatory response [2, 40, 41]

Summary

Introduction

Bovine mastitis is one of the most common diseases in dairy farming, which causes great economic losses to the world dairy industry [1]. Mastitis caused by pathogenic bacteria is the most common in daily productions. Gram-negative bacteria such as Escherichia coli can cause severe mastitis in dairy cows, seriously affecting the health and milk quality of cows [2]. Lipopolysaccharide (LPS) is an active component of the cell wall of gram-negative bacteria. When these bacteria rupture, they enter the animal body and promote the development of inflammation [3]. LPS is regarded as the major factor to induce mastitis when cows are infected by gram-negative bacteria in mammary gland. Macrophages are present in the mammary gland interstitium and acinus cells protecting mammary epithelium against invading microorganisms [5]. Macrophages in the mammary gland are an essential immunological defense mechanism against infection in the innate immune system

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