Neutrophil Extracellular Traps Mediate Bovine Endometrial Epithelial Cell Pyroptosis in Dairy Cows with Endometritis

Int J Mol Sci. 2022 Nov 13;23(22):14013. doi: 10.3390/ijms232214013.

Abstract

Neutrophils are involved in the development of endometritis, but it remains unknown how neutrophils induce inflammation and tissue damage. Neutrophil extracellular traps (NETs) clear invading pathogens during infection but induce pyroptosis, leading to inflammation and tissue damage. Thus, our objective was to investigate whether NETs participate in bovine endometrial epithelial cell (BEEC) pyroptosis during endometritis. To confirm this, NETs and caspase-1/4; apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC); nod-like receptor protein-3 (NLRP3); and gasdermin D N-terminal (GSDMD-N), TNF-a, IL-1β, IL-6, and IL-18 in endometrial tissue were detected. Pathological section and vaginal discharge smears were performed to visually determine endometritis in the uterus. BEECs were stimulated with NETs to induce pyroptosis, which was treated with DNase I against pyroptosis. Caspase-1/4, ASC, NLRP3, GSDMD-N, TNF-a, IL-1β, IL-6, and IL-18 in BEECs were analyzed in endometrial tissue. The results showed that NET formation, as well as pyroptosis-related proteins and proinflammatory, cytokines were elevated in the endometrial tissue of cows with endometritis. Pathological sections and vaginal discharge smears showed increased neutrophils and plasma cells in the uterus, as well as tissue congestion. In BEECs, NETs increased the level of pyroptosis-related proteins and proinflammatory cytokines and were diminished by DNase I. In summary NETs participate BEEC pyroptosis during endometritis in dairy cows.

Keywords: BEECs; NETs; dairy cow; endometritis; pyroptosis.

MeSH terms

  • Animals
  • Cattle
  • Cytokines / metabolism
  • Deoxyribonuclease I / metabolism
  • Endometritis* / veterinary
  • Epithelial Cells / metabolism
  • Extracellular Traps* / metabolism
  • Female
  • Humans
  • Inflammation
  • Interleukin-18 / metabolism
  • Interleukin-6 / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • NLR Proteins / metabolism
  • Phosphate-Binding Proteins / metabolism
  • Pyroptosis
  • Vaginal Discharge*

Substances

  • Interleukin-18
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Phosphate-Binding Proteins
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • NLR Proteins
  • Cytokines
  • Deoxyribonuclease I