Melatonin Maintains Homeostasis and Potentiates the Anti-inflammatory Response in -Induced Mastitis through microRNA-16b/YAP1.

is a highly infectious pathogen and is a considerable threat to food hygiene and safety. Although melatonin is thought to exert an ameliorative effect on bovine mastitis, the regulatory mechanisms are unclear. In this study, we first verified the therapeutic effect of melatonin against in vitro and in vivo, a screening of differentially expressed miRNAs and mRNAs among the blank, and and melatonin + groups by high-throughput sequencing identified miR-16b and , which exhibited 1.95-fold upregulated and 1.05-fold downregulated expression, respectively. Moreover, epigenetic studies showed that inhibited miR-16b expression by methylation (increased DNMT1 expression). Additionally, the expression level was significantly decreased by melatonin treatment, which might indicate that the inhibition of by melatonin reduces the effect of on miR-16b. The flow cytometry, scanning and transmission electron microscopy, EdU assay, and cell morphology results indicated that miR-16b in bovine mammary epithelial cells (in vitro) and in mice (in vivo) can modulate the maintenance of homeostasis and potentiate the anti-inflammatory response. In addition, was demonstrated to be the target gene of miR-16b through quantitative real-time polymerase chain reaction, western blot, RNA immunoprecipitation, and functional assays. This study indicates that melatonin inhibits -induced inflammation via microRNA-16b/-mediated regulation, and these findings might provide a new strategy for the prevention of bovine mastitis, facilitating further studies good of zoonotic diseases caused by infection.