Abstract
Mastitis, an inflammatory disease, causes severe economic loss in the dairy industry, which is mainly infected by bacteria. Staphylococcus aureus (S. aureus), the major pathogenic microorganism, derived from lipoteichoic acid (LTA) has been identified to activate inflammatory responses, but the cellular or intercellular regulatory mechanism is unclear. This study mainly focused on the effects of LTA in bovine mammary epithelial cells (Mac-T) and elaborated the regulation of microRNAs (miRNAs). The results showed that LTA enhanced the messenger RNA (mRNA) expression and production of tumor necrosis factor α (TNF-α) and interleukin (IL)-6. Furthermore, LTA could activate Toll-like receptor (TLR)2/MyD88-mediated phosphoinositide 3-kinase (PI3K)/AKT pathway, and TLR2 plays a pivotal role in LTA-induced inflammatory responses. The results of qRT-PCR showed that miRNA levels increased and reached the highest at 3 h and then gradually decreased over time in Mac-T cells. In exosomes, the levels of 11 and three miRNAs were upregulated and downregulated at 24 h, respectively. In addition, miR-23a showed the highest increase in Mac-T cells treated with LTA and targeted PI3K to regulate inflammatory responses. Furthermore, Mac-T cell-derived exosomes were identified to play a cell–cell communication by promoting M1 polarization of bovine macrophages. In summary, our study demonstrated that LTA could activate inflammatory responses via TLR2/MyD88/PI3K/AKT signaling pathway, and miR-23a inhibited it by targeting PI3K. Furthermore, we found that Mac-T cell-derived exosomes might be associated with inflammatory responses by promoting M1 polarization of bovine macrophages.
Highlights
Mastitis is one of the most common diseases in the dairy industry, which causes ∼2-billion-dollar losses a year due to reduced milk production and changes in milk composition, treatment, veterinary costs, and replacement animal costs in the US [1]
Cells were incubated at 37◦C in the presence of 5% CO2 with 100 ng/ml granulocyte–macrophage colonystimulating factor (GM-CSF; abcam, USA) for 3 days, the medium was replaced with fresh culture medium with GM-CSF for 5 extra days to induce cell differentiation into macrophages
The results indicated that Lipoteichoic acid (LTA) induced an upregulation of tumor necrosis factor α (TNF-α) messenger RNA (mRNA) level at 1 and 3 h but showed no significant difference (p > 0.05) (Figure 1A)
Summary
Mastitis is one of the most common diseases in the dairy industry, which causes ∼2-billion-dollar losses a year due to reduced milk production and changes in milk composition, treatment, veterinary costs, and replacement animal costs in the US [1]. Regulation in S. aureus Induced Inflammation further analysis of the regulatory mechanism of S. aureusinfected mastitis is very important for effective therapies. Some genes, such as tumor necrosis factor α (TNF-α) and basic fibroblast growth factor (bFGF), are identified to be associated with inflammation in bovine mammary epithelial cells (bMECs; MacT) [10]. BMECs play an important role in bacterial infection and secrete a plethora of cytokines and other inflammatory mediators after being stimulated by bacterial toxins, such as cell wall components, to cause mastitis. It is important to reveal the mechanisms of host immunity in bacteria-infected mammary epithelial cells. Few studies focused on the regulatory mechanisms of TLR2-mediated activation of PI3K-AKT pathway in LTAinfected bMECs
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