An underlying mechanism of bovine mastitis: PGEregulates-induced inflammatory response through TLR2, TLR4, and NLRP3 in macrophages.

Abstract

() evades host immunity by modulating macrophage functions, including immune regulation and phagocytosis, ultimately contributing to bovine mastitis. This study aimed to elucidate the molecular mechanisms of-induced bovine mastitis from both host and pathogen perspectives, focusing on prostaglandin E(PGE) as a key regulator. During bovine mastitis, macrophages were recruited into the mammary gland with elevated inflammatory mediators.lipoproteins amplified inflammation by activating MAPK and NF-κB pathwaysTLR2, TLR4, and NLRP3, leading to elevated secretion of mediators, including PGE, in bBMMs. Inhibition of TLR2, TLR4, or NLRP3 decreased COX-2 and mPGES-1 expression, suppressing PGEsynthesis, while inhibition of COX-2 or mPGES-1 can regulate the expression of TLR2 and NLRP3, as well as the activation of MAPKs and NF-κB signaling pathways. Excess PGEcan regulate inflammation and phagocytosis mediated by TLR2, TLR4, and NLRP3.lipoproteins promote PGEsynthesisTLR2, TLR4, and NLRP3 signaling, while PGE, in turn, modulates receptor activity, inflammation, and phagocytosis. These findings reveal crucial functional cross-talk between PGEand innate immune receptors in-induced mastitis, suggesting that targeting this interaction may provide novel therapeutic strategies.