Prostaglandin E2 stimulates anion and fluid secretion triggered by lipopolysaccharide in rat vaginal epithelium

Mol Cell Endocrinol. 2021 Apr 15:526:111219. doi: 10.1016/j.mce.2021.111219. Epub 2021 Feb 19.

Abstract

Prostaglandin E2 (PGE2) is a principal lipid mediator mediating various biological processes including immune responses and fluid secretion. As the first line of host defense against infection, vaginal epithelium plays orchestrated roles in vaginal innate immunity. However, the effect of PGE2 triggered by pro-inflammatory stimuli on vaginal epithelium remains elusive. This study aimed to investigate the regulatory role of PGE2 on vaginal epithelium after lipopolysaccharide (LPS) stimulation. RT-PCR and western blot analysis revealed that E-prostanoid (EP) receptors EP2 and EP4 were expressed in rat vagina. Basolateral application of PGE2 induced anion secretion mediated by cystic fibrosis transmembrane conductance regulator (CFTR) via EP-adenylate cyclase-cAMP signaling pathway in rat vaginal epithelial cells. The in vivo study showed that PGE2 promoted fluid secretion in rat vagina. Moreover, LPS stimulation facilitated cyclooxygenase-dependent PGE2 synthesis and vaginal fluid secretion in vivo. Conclusively, LPS stimulation triggered epithelium-derived PGE2 production in vaginal epithelium, leading to CFTR-mediated anion secretion and luminal flushing. This study provides valuable insights into the physiological role of PGE2 during vaginal bacterial infection.

Keywords: Bacterial infection; Cystic fibrosis transmembrane conductance regulator; Luminal flushing; Prostaglandin E2; Vaginal epithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anions
  • Body Fluids / drug effects
  • Body Fluids / metabolism*
  • Cyclic AMP / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Dinoprostone / pharmacology*
  • Electrophysiological Phenomena / drug effects
  • Epithelium / drug effects
  • Epithelium / metabolism*
  • Female
  • Lipopolysaccharides / pharmacology*
  • Models, Biological
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Prostaglandin E, EP2 Subtype / metabolism
  • Receptors, Prostaglandin E, EP4 Subtype / metabolism
  • Signal Transduction / drug effects
  • Solute Carrier Family 12, Member 2 / metabolism
  • Vagina / drug effects
  • Vagina / metabolism*

Substances

  • Anions
  • Lipopolysaccharides
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Solute Carrier Family 12, Member 2
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cyclic AMP
  • Dinoprostone