LP induced/mediated PGE synthesis through activation of the ERK/NF-κB pathway contributes to inflammatory damage triggered by Escherichia coli-infection in bovine endometrial tissue.

The bovine endometrium is constantly challenged with pathogenic bacteria, especially with Escherichia coli. In previous studies, we showed that prostaglandin E (PGE) synthesis was increased in E. coli-infected bovine endometrial tissue, which promoted the development of inflammatory damage. However, the molecular mechanism underlying this accumulation of PGE remained undefined. Lipoprotein (LP) is one of critical outer membrane protein in E. coli, which regulates inflammatory response. In this study, we determined the role of LP in PGE accumulation in bovine endometrial tissue by infecting the tissue with wild endometrial pathogenic E. coli and E. coli LP deletion mutant (JE5505) strains. We demonstrate that JE5505 was less effective than pathogenic E. coli in inducing the production of PGEIL-6, TNF-α, HMGB-1, and HABP1 and that the induction of cytokines was dependent on the activation of MAPKs, as revealed by rapid phosphorylation of ERK1/2/NF-κB in the endometrial tissues, furthermore, LP also induced PGE synthessis and cytokine secretion. Additionally, ERK and NF-κB inhibitors significantly inhibited PGE production and cytokine secretion and reduced or attenuated tissue damage in JE5505-infected and LP induced endometrial tissues. What is more important, we reported PGE introduction increased the expression of pro-inflammatory factors and DAMPs in E. coli-infected bovine endometrial tissue. Taken together, these results indicate that LP is involved in the accumulation of PGE through the activation of the ERK/NF-κB pathway that induces the production of pro-inflammatory factors and damage-associated molecular patterns (DAMPs) in E. coli-infected bovine endometrial tissue. These results should help in better understanding and management of postpartum inflammatory diseases in dairy cows.