Abstract
Simple SummaryBovine mastitis results in substantial problems in terms of animal health, food safety, and profitability of farmers. Methionyl-methionine dipeptide confers protection in the bovine mammary epithelial cells as evidenced by our previous transcriptomic study at the molecular level. However, whether the metabolic production of Met-Met confers protection remains unknown. In this study, Met-Met significantly suppressed LPS-induced TNF-α, IL-8, AP-1, and MCP-1 expression; reversed decreased tryptophan, phenylalanine, and histidine levels; and inhibited LPS-induced palmitic acid and stearic acid levels as well as purine metabolism disorder. Overlapping metabolites were mainly involved in the cysteine and methionine metabolism, fatty acids biosynthesis, and purines degradation. These metabolites and pathways might contribute to the protective action of methionyl-methionine.Our previous transcriptomic study found that methionyl-methionine (Met-Met) exerts an anti-inflammatory effect in the bovine mammary epithelial cell (MAC-T) at a molecular level. However, evidence of whether the metabolic production of Met-Met confers protection was scarce. To investigate the inflammatory response and metabolite changes of Met-Met in lipopolysaccharide (LPS)-induced inflammation of MAC-T, mass spectrometry-based metabolomics and qPCR were conducted. The increased levels of IL-8, TNF-α, AP-1, and MCP-1 were reduced by pretreating with 2 mM Met-Met after LPS exposure. Metabolomics profiling analysis demonstrated that LPS induced significant alteration of metabolites, including decreased tryptophan, phenylalanine, and histidine levels and increased palmitic acid and stearic acid levels as well as purine metabolism disorder, whereas Met-Met reversed these changes significantly. Pathways analysis revealed that overlapping metabolites were mainly enriched in the cysteine and methionine metabolism, fatty acids biosynthesis, and purines degradation. Correlation networks showed that the metabolic profile was significantly altered under the conditions of inflammation and Met-Met treatment. Collectively, Met-Met might relieve MAC-T cell inflammation via hydrolysate methionine, which further changes the processes of amino acid, purine, and fatty acid metabolism.
Highlights
Lipopolysaccharide can bind to toll-like acceptor 4 (TRL4) receptors on the cell membrane of bovine mammary epithelial cells (MAC-T), and further activate the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways to induce mastitis [3,4]
The level of MCP-1 was suppressed at 1 h (0.53 ± 0.19 vs. 1.29 ± 0.36, p < 0.05) (Figure 1A) in the Met-Met+LPS group when compared with the LPS group; this suppression of MCP-1 by Met-Met decreased over time (Figure 1B–D)
Compared with the control group, Met-Met treatment alone significantly suppressed the expression of TNF-α, IL-8, AP-1, and MCP-1 at 1 and 3 h (Figure 1A,B)
Summary
With the intensive development of the dairy industry, mastitis caused by Gramnegative bacteria in the environment has attracted much attention [1]. For this reason, the pathogenic mechanism of Gram-negative bacteria in dairy cows is fundamental to control bovine mastitis. Previous studies have shown that lipopolysaccharide (LPS), as the main component of the cell wall of Gram-negative bacteria, is an important part of inducing mastitis in dairy cows [2]. Several efficient programs are utilized to control bovine mastitis. Despite the fulfillment of control programs, the commonness of bovine mastitis is a major problem. A study focusing on improving cow immunity by nutritional additives, such as dipeptides, instead of drug treatment is superior
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