Prostaglandin E2 promotes Pam3CSK4-induced inflammation in endometrial epithelial cells of cattle.

Bacterial contamination often impairs uterine function in cattle leading to uterine diseases such as endometritis. Inflammatory responses to bacterial infections in the uterus of cattle are generated through pattern recognition receptors, including Toll-like receptor 2 (TLR2), which is responsible for Pam3CSK4 recognition. This cellular response induces inflammatory responses through stimulation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling activation, stimulating the expression of inflammatory mediators. Prostaglandin (PG) E2 has important actions in bacterial endometritis, although details through which these mechanisms regulate Pam3CSK4-induced inflammatory responses in cattle endometrial epithelial cells (bEECs) remain unclear. In the present study there was examination of the actions of exogenous PGE2 in Pam3CSK4-induced inflammatory responses. The bEECs pre-treated with exogenous PGE2 prior to Pam3CSK4 treatment had an augmented Pam3CSK4-stimulated phosphorylation of protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and IκB-α; stimulation of TLR2, cyclooxygenase-2, and interleukin-6 functions; and suppression of the activation of PGE2 receptor 4. Thus, Pam3CSK4-induced inflammatory responses through TLR2 signaling in bEECs were enhanced by exogenous PGE2 pre-treatment.