| Dairy cow endometriti is the most common reproductive system disease in dairy cows,which is the main cause of the decline in the fertility of cows,posing a serious threat to the development of dairy farming.Escherichia coli(E.coli)has been identified as an important microorganism causing endometritis,and its bacterial component lipopolysaccharide(LPS)is involved in the pathogenic process of postpartum endometritis in cows,causing a series of inflammatory responses;In addition to LPS,Braun lipoprotein(BLP),another component in the outer membrane of E.coli,also plays an important role in inducing inflammatory response,and BLP binds to TLR2 receptors on the cell membrane surface,which in turn triggers the activation of JNK and p38 mitogen-activated protein kinase MAPK family and NF-κB signaling pathway,causing the secretion of a series of cytokines.Studies have shown that in addition to their ability to induce host inflammatory responses,bacterial lipoprotein also plays a key role in regulating host immune responses and inflammatory response intensity.Studies have shown that hosts can downregulate the expression of proinflammatory cytokines in vivo through tolerance to synthetic bacterial lipoprotein Pam3CSK4,thereby promoting their own effective protection against LPS stimulation,bacterial infection and sepsis.However,the mechanism of BLP on E.coli inducing endometrial inflammatory response in dairy cows remains unclear.In this experiment,LPS,BLP and LPS combined with BLP were used.E.coli DH5α,E.coli JE5505 and E.coli JE5505 were combined with BLP to infect epithelial cells and tissues.The cytokine secretion and gene expression levels in epithelial cells and tissues,the activation of inflammatory and anti-inflammatory signaling pathways in cells,the effect of TLR2 receptor activation on cytokine secretion,and the damage and regulation of BLP on tissues infected by LPS or E coli were studied.The results indicated that BLP combined with TLR2 may reduce the production of pro-inflammatory factors and chemokines in cow endometrial epithelial cells depending on the activation of MAPK and NF-κB signaling pathways,and may increase the production of anti-inflammatory factor IL-10 by activating STAT3 signaling pathway.Thus,the host can form tolerance and plays a protective role against LPS or E coli induced inflammation of cow endometrial epithelial cells and tissues.In conclusion,BLP can regulate the production of pro-inflammatory and antiinflammatory cytokines through the involvement of TLR2 in MAPK,NF-κB and STAT3 signaling pathways,and this tolerance can reduce the severity of endometrial tissue damage in dairy cows.These results suggest that BLP-induced tolerance may be involved in the immune response induced by E coli in cow endometrial epithelial cells and tissues,providing a new strategy for combating bacterial infection. |