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

Wu, Yongjiang; Sun, Yawang; Dong, Xianwen; Wang, Zili; Chen, Juncai; Dong, Guozhong

doi:10.3390/toxins12060387

Cited by 17 publications

(16 citation statements)

References 55 publications

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“…The expression of cytokines displayed an overall increase, when LPS concentration was raised to 0.1 μg/mL. In our previous study, 0.1 μg/mL LPS induced an overall increase in the expression of cytokines [ 43 ] and caused hypomethylation of genes involved in the immune pathways [ 44 ], which successfully promoted inflammatory responses of BMECs. In a study by Guenther et al [ 38 ], they found that 0.1 μg/mL LPS enhanced the expression of inflammatory factors, including IL-8 and C-C motif chemokine ( CCL ) 5 .…”

Section: Discussionmentioning

confidence: 99%

Effects of Peptidoglycan, Lipoteichoic Acid and Lipopolysaccharide on Inflammation, Proliferation and Milk Fat Synthesis in Bovine Mammary Epithelial Cells

Sun

Zhu

et al. 2020

Toxins

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The mammary gland of the cow is particularly susceptible to infections of a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative bacteria. The endotoxins of these pathogenic bacteria include peptidoglycan (PGN), lipoteichoic acid (LTA) and lipopolysaccharide (LPS), and they are the pathogen-associated molecular patterns (PAMPs) to induce mastitis. LPS can directly inhibit proliferation and milk fat synthesis of bovine mammary epithelial cells (BMECs) while inducing mastitis, but it is unclear whether PGN and LTA also have such effects. Furthermore, since the three PAMPs usually appear simultaneously in the udder of cows with mastitis, their synergistic effects on proliferation and milk fat synthesis of BMECs are worth investigating. The immortalized BMECs (MAC-T cells) were stimulated for 24 h using various concentrations of PGN, LTA and LPS, respectively, to determine the doses that could effectively cause inflammatory responses. Next, the cells were stimulated for 24 h with no endotoxins (CON), PGN, LTA, LPS, PGN + LTA, and PGN + LTA + LPS, respectively, with the predetermined doses to analyze their effects on proliferation and milk fat synthesis of BMECs. PGN, LTA and LPS successfully induced inflammatory responses of BMECs with doses of 30, 30 and 0.1 μg/mL, respectively. Although the proliferation of BMECs was significantly inhibited in the following order: LTA < PGN + LTA < PGN + LTA + LPS, there was no change in cell morphology and cell death. LTA significantly promoted the expression of fatty acid synthesis-related genes but did not change the content of intracellular triglyceride (TG), compared with the CON group. The mRNA expression of fatty acid synthesis-related genes in the LPS group was the lowest among all the groups. Meanwhile, LPS significantly decreased the content of intracellular non-esterified fatty acids (NEFAs) and TG, compared with the CON group. PGN had no effects on milk fat synthesis. Co-stimulation with PGN, LTA and LPS significantly increased the expression of fat acid synthesis-related genes and the intracellular NEFAs, but decreased intracellular TG, compared with sole LPS stimulation. Collectively, PGN, LTA and LPS showed an additive effect on inhibiting proliferation of BMECs. The promoting role of LTA in fatty acid synthesis might offset the negative effects of LPS in this regard, but co-stimulation with PGN, LTA and LPS significantly decreased intracellular TG content.

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Section: Discussionmentioning

confidence: 99%

Effects of Peptidoglycan, Lipoteichoic Acid and Lipopolysaccharide on Inflammation, Proliferation and Milk Fat Synthesis in Bovine Mammary Epithelial Cells

Sun

Zhu

et al. 2020

Toxins

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Section: Discussionmentioning

confidence: 99%

“…LPS, PGN and LTA are PAMPs [ 5 , 6 ]. All of them can act as antigens and will induce an inflammatory response if present in the peripheral blood, resulting in injury to the body cells and tissues [ 5 , 6 ]. High concentration of LPS induced by HC diet usually results in ruminal epithelium injury, such as inflammation [ 42 ], apoptosis, high osmolarity [ 43 ], etc.…”

Section: Discussionmentioning

confidence: 99%

“…Bacterial cell wall components mainly include lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria (GNB) [ 3 ]; lipoteichoic acid (LTA), the endotoxin of Gram-positive bacteria (GPB) [ 3 ]; and peptidoglycan (PGN), the structural polysaccharide from both GNB and GPB [ 4 , 5 ]. LPS, LTA and PGN are pathogen-associated molecular patterns (PAMPs) [ 5 , 6 ], and thus they can activate corresponding pattern recognition receptors (PRRs) [ 7 , 8 , 9 ]. LPS, LTA and PGN predominantly activate Toll-like receptor (TLR) 4 [ 7 ], TLR2 [ 8 ] and nucleotide-binding oligomerization domain (NOD) 1 [ 9 ], respectively, resulting in inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

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Sodium Butyrate More Effectively Mitigates the Negative Effects of High-Concentrate Diet in Dairy Cows than Sodium β-Hydroxybutyrate via Reducing Free Bacterial Cell Wall Components in Rumen Fluid and Plasma

Sun

Zhang

et al. 2021

Toxins

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The present study was aimed at investigating the effects of sodium butyrate and sodium β-hydroxybutyrate on lactation and health of dairy cows fed a high-concentrate (HC) diet. Eighty mid-lactation dairy cows with an average milk yield of 33.75 ± 5.22 kg/d were randomly allocated to four groups (n = 20 per group) and were fed either a low-concentrate (LC) diet, a HC diet, the HC diet with 1% sodium butyrate (HCSB), or the HC diet with 1% sodium β-hydroxybutyrate (HCHB). The feeding trial lasted for 7 weeks, with a 2-week adaptation period and a 5-week measurement period, and the trial started from 96 ± 13 d in milk. Sodium butyrate supplementation delayed the decline in milk production and improved milk synthesis efficiency and milk fat content. Additionally, it decreased the proinflammatory cytokines and acute phase proteins (APPs) in plasma, the leucocytes in blood, the somatic cell count (SCC) in milk, and the gene expression of pattern recognition receptors (PRRs) and proinflammatory cytokines in the mammary gland, due to decreasing the contents of bacterial cell wall components (lipopolysaccharide, LPS; peptidoglycan, PGN; and lipoteichoic acid, LTA) in the rumen and plasma, compared with the HC diet. Sodium β-hydroxybutyrate supplementation also improved milk yield, milk synthesis efficiency and milk fat content and partially reduced the adverse effects caused by the HC diet, but it had no effect on decreasing bacterial cell wall components in the rumen and plasma, compared with the HC diet. Collectively, both sodium butyrate and sodium β-hydroxybutyrate mitigated the negative effects of HC diet on lactation and health of dairy cows, with sodium butyrate being more effective than sodium β-hydroxybutyrate.

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“…DNA methylation was reported to regulate the expression of IL-6R rather than genetic mutations in response to mastitic pathogen ( Zhang et al, 2018a ). Moreover, the co-stimulation of bovine mammary epithelial cells with LPS, peptidoglycan (PGN), and lipoteichoic acid (LTA) significantly increased DNA hypomethylation compared with LPS stimulation, indicating that the additive effects of co-stimulation decreased methylation levels resulting in increased transcriptome changes and inflammatory responses ( Wu et al, 2020c ). The hypermethylation of the CD4 promoter was reported to repress its gene expression in Holstein cows with clinical mastitis ( Wang et al, 2013 ; Usman et al, 2016 ).…”

Section: Evidence Of the Impacts Of Epigenetic Processes On Livestockmentioning

confidence: 99%

Impacts of Epigenetic Processes on the Health and Productivity of Livestock

Wang

Ibeagha‐Awemu

2021

Front. Genet.

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The dynamic changes in the epigenome resulting from the intricate interactions of genetic and environmental factors play crucial roles in individual growth and development. Numerous studies in plants, rodents, and humans have provided evidence of the regulatory roles of epigenetic processes in health and disease. There is increasing pressure to increase livestock production in light of increasing food needs of an expanding human population and environment challenges, but there is limited related epigenetic data on livestock to complement genomic information and support advances in improvement breeding and health management. This review examines the recent discoveries on epigenetic processes due to DNA methylation, histone modification, and chromatin remodeling and their impacts on health and production traits in farm animals, including bovine, swine, sheep, goat, and poultry species. Most of the reports focused on epigenome profiling at the genome-wide or specific genic regions in response to developmental processes, environmental stressors, nutrition, and disease pathogens. The bulk of available data mainly characterized the epigenetic markers in tissues/organs or in relation to traits and detection of epigenetic regulatory mechanisms underlying livestock phenotype diversity. However, available data is inadequate to support gainful exploitation of epigenetic processes for improved animal health and productivity management. Increased research effort, which is vital to elucidate how epigenetic mechanisms affect the health and productivity of livestock, is currently limited due to several factors including lack of adequate analytical tools. In this review, we (1) summarize available evidence of the impacts of epigenetic processes on livestock production and health traits, (2) discuss the application of epigenetics data in livestock production, and (3) present gaps in livestock epigenetics research. Knowledge of the epigenetic factors influencing livestock health and productivity is vital for the management and improvement of livestock productivity.

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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

Cited by 17 publications

References 55 publications

Effects of Peptidoglycan, Lipoteichoic Acid and Lipopolysaccharide on Inflammation, Proliferation and Milk Fat Synthesis in Bovine Mammary Epithelial Cells

Effects of Peptidoglycan, Lipoteichoic Acid and Lipopolysaccharide on Inflammation, Proliferation and Milk Fat Synthesis in Bovine Mammary Epithelial Cells

Sodium Butyrate More Effectively Mitigates the Negative Effects of High-Concentrate Diet in Dairy Cows than Sodium β-Hydroxybutyrate via Reducing Free Bacterial Cell Wall Components in Rumen Fluid and Plasma

Impacts of Epigenetic Processes on the Health and Productivity of Livestock

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