Bacterial endotoxin decreased histone H3 acetylation of bovine mammary epithelial cells and the adverse effect was suppressed by sodium butyrate

Abstract

Background In practical production, dairy cows are frequently exposed to bacterial endotoxin (lipopolysaccharide, LPS) when they are subjected to high-concentrate diets, poor hygienic environments, as well as mastitis and metritis. Histone acetylation is an important epigenetic control of DNA transcription and a higher histone acetylation is associated with facilitated transcription. LPS might reduce histone acetylation in the mammary epithelial cells, resulting in lower transcription and mRNA expression of lactation-related genes. This study was conducted to investigate the effect of LPS on histone acetylation in bovine mammary epithelial cells and the efficacy of sodium butyrate (SB) in suppressing the endotoxin-induced adverse effect. Firstly, the bovine mammary epithelial cell line MAC-T cells were treated for 48 h with LPS at different doses of 0, 1, 10, 100, and 1000 endotoxin units (EU)/mL (1 EU = 0.1 ng), and the acetylation levels of histones H3 and H4 as well as the histone deacetylase (HDAC) activity were measured. Secondly, the MAC-T cells were treated for 48 h as follows: control, LPS (100 EU/mL), and LPS (100 EU/mL) plus SB (10 mmol/L), and the acetylation levels of histones H3 and H4 as well as milk gene mRNA expressions were determined. Results The results showed that HDAC activity increased linearly with increasing LPS doses ( P < 0.01). The histone H3 acetylation levels were significantly reduced by LPS, while the histone H4 acetylation levels were not affected by LPS ( P > 0.05). Sodium butyrate, an inhibitor of HDAC, effectively suppressed the endotoxin-induced decline of histone H3 acetylation ( P < 0.05). As a result, SB significantly enhanced the mRNA expression of lactation-related genes ( P < 0.05). Conclusions The results suggest one of the adverse effects of LPS on the lactation of bovine mammary gland epithelial cells was due to decreasing histone H3 acetylation through increasing HDAC activity, whereas the endotoxin-induced adverse effects were effectively suppressed by SB. Electronic supplementary material The online version of this article (10.1186/s12917-019-2007-5) contains supplementary material, which is available to authorized users.

PGN and LTA from Staphylococcus aureus Induced Inflammation and Decreased Lactation through Regulating DNA Methylation and Histone H3 Acetylation in Bovine Mammary Epithelial Cells

“…At the same time, compared with the CON group, the relative mRNA expression of CSN1 and CSN2 significantly decreased and the relative mRNA expression of CSN3 also decreased numerically. Our previous study showed that LPS suppressed lactation-related gene expression due to reducing histones H3 acetylation by enhancing HDAC activity [16]. Taken together, our results revealed that PGN and LTA reduced histone H3 acetylation through regulating HAT and HDAC activity, which might result in lower mRNA expression of caseins.…”

“…Our previous study showed that LPS enhanced immune responses of bovine mammary epithelial cells by decreasing DNA methylation [15]. Moreover, our other study indicated that LPS reduced histone H3 acetylation through enhancing HDAC activity, and subsequently suppressed the expression of lactation-related genes, such as acetyl coenzyme-A carboxylase 1 (ACACA), fatty acid synthase (FASN), and ribosomal protein S6 kinase 1 (S6K1) [16]. Like E. coli, S. aureus could induce bovine subclinical mastitis by regulating DNA methylation [17][18][19].…”

The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells

“…Persistent peripheral presence of S. aureus reduced histone H3 acetylation in rat brain tissues [ 55 ]. In addition to the direct effects of bacterial pathogens on histone acetylation, we found in our previous study that LPS (0.1 μg/mL) could suppress lactation-related gene expression through reducing histone H3 acetylation by enhancing HDAC activity in BMECs [ 39 ]. In this study, LPS (0.1 μg/mL) significantly decreased histone H3 acetylation and the expression of three caseins, which was consistent with our previous research.…”

“…Other studies have also shown that LTA and PGN could cause the DNA hypomethylation of the key regulators of inflammatory pathways, promoting the release of a variety of inflammatory factors [37,38]. In addition, our previous studies showed that LPS, LTA, and PGN suppressed the expression of lactation-related genes of BMECs due to reducing histone H3 acetylation through regulating HAT and HDAC activity [19,39]. Thus, we speculated that co-stimulation with LPS, LTA, and PGN might have an additive effect on DNA hypomethylation and histone hypoacetylation, producing a more intense inflammatory response and decreasing casein expression to a greater degree than single stimulation of either of the PAMPs in BMECs.…”

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

“…Histone octamer and DNA constitute nucleosomes, which are free in the N-terminal of the nucleosome and can accept various modifications, including acetylation and deacetylation (63,64). Active histones H4 and H3 acetylate lysine residues under the action of histone acetyltransferase, which facilitates chromatin expression, while histone deacetylase acts contrary and blocks chromatin expression (65). Acetylation and deacetylation of histones are dynamic.…”