The Regulation Of IFN-tau For Staphylococcus Aureus Induced Endometrial Inflammation Response By NF-κB Signal Transduction Pathway In Mice

Endometritis is usually the uterine inflammation of animals.endometritis have a high incidence,that is about 20%—40%.Endometritis could affect the milk production of cows,and made it lower than the healthy cows’ milk.This could increase cows’ feed cost and rate of replacement,and cause huge ecomomic losses.Staphylococcus aureus is common pathogenic bacteria of endometritis in dairy cows.The main clinical use of antibiotics for treatment of Staphylococcus aureus.However,the drug resistance and drug residues may lead to serious food safety problems.If we use the cows as experimental animals in our study,it will spend a lot of experiment funds,And this is not also accord with the requirements of experimental mechanism.In order to make the endometritis of mouse model,we use the microsyringe to intrauterine injection of Staphylococcus aureus bacteria in the uterine of mice.These could help us further understand the mechanism of endometritis,and contribute to the treatment of endometritis..IFN-tau,belongs to the type I interferon,is secreted by the trophoblast cells during the ruminants pregnancy.It could highly resistant to dissolution of corpus luteum,antiviral,anti-biological functions,such as cell proliferation,immunomodulation,particularly the immunomodulatory activity of autoimmune diseases and low cytotoxicity.These characteristics make it become a new type of medicine.Toll-like receptor 2(TLR2)is a kind of pattern recognition receptors which have involved in immune defense(PRR).When the animals have suffered from endometritis,the extracellular matrix will be changed,such as Metalloproteinase 9(MMP9)and TIMP1 which is the natural tissue inhibitor of MMP9.In our study,we had chosen 40 healthy female BALB/c mice as the experiment animals.And these mice were randomly divided into 4 groups,respectively control group,aureus group,IFN-tau control group and IFN-tau + aureus group.We use Staphylococcus aureus infect mice in the aureus group and IFN-tau + aureus group.While control group and IFN-tau control group using Sodium Chloride Solution in the same way.After 24 h,IFN-tau control group and IFN-tau + aureus group were injected intraperitoneally 8 ng/g IFN-tau(0,8,16h).Finally,we collected samples of the mice uterus.Experimental results show that:1.IFN-tau could reduce the inflammation of the mice uterine tissue caused by Staphylococcus aureus.But it has no effect against Staphylococcus aureus.In order to further corroborate experimental results.In our study,we isolation and culture of mouse endomertrium epithelial cells(mEECs),after stimulated by Staphylococcus aureus,the experimental results are consistent with results of animal experiments.2.In order to further research the anti-inflammatory mechanism of the IFN-tau.We had in-depth studied of the regulation of signaling proteins.Results show that IFN-tau could induce the expression of TLR2 and reduce the activation of the downstream signals of TLR2.We research the downstream of NF-κB signaling pathway shows that IFN-tau could reduce the expression of the phosphorylation IκBα and P65 and inhibit the expression of IL-1β,TNF-α and IL-6.3.In order to research the changes of extracellular matrix of the mice uterus.In our study,We had chosen qPCR and western blot to detect the expression of TIMP1 and MMP9.Results show that IFN-tau could induce the expression of MMP9.Conclusion: This paper mainly studies the therapeutic effect and mechanism of IFN-tau on Staphylococcus aureus induced endometritis in mice: The results show that IFN-tau can mediate TLR2/NF-κB inflammatory signaling pathway,lower the expression of TLR2 and NF-κB p65,thus IFN-tau could inhibit the release of inflammatory factors and reduce the inflammation injury of tissue.