Allergy Asthma Immunol Res.  2013 Jul;5(4):224-231. 10.4168/aair.2013.5.4.224.

Effect of Prostaglandin E2 on Vascular Endothelial Growth Factor Production in Nasal Polyp Fibroblasts

Affiliations
  • 1Department of Otolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan, Korea. bjbaek@schmc.ac.kr
  • 2Division of Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Seoul, Korea.
  • 3Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Angiogenesis is involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. We aimed to investigate the effects of prostaglandin E2 (PGE2) on vascular endothelial growth factor (VEGF) production, the role of E-prostanoid (EP) 4 receptors, and the signal transduction pathway mediating VEGF production in nasal polyp-derived fibroblasts (NPDFs).
METHODS
Eight primary NPDF cultures were established from nasal polyps, which were incubated with or without PGE2. Reverse transcription-polymerase chain reaction amplification of EP receptors (EP1, EP2, EP3, and EP4) and immunofluorescence staining for VEGF production were performed. VEGF production via the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) pathways was evaluated by enzyme-linked immunosorbent assay.
RESULTS
All EP receptors were expressed in NPDFs. PGE2 significantly increased VEGF production concentration- and time dependently, and VEGF production was regulated by an EP4 receptor. Activation of intracellular cAMP regulated VEGF production. VEGF production was decreased by PKA and PI3K inhibitors via intracellular cAMP.
CONCLUSIONS
PGE2 stimulates VEGF production via the EP4 receptor in NPDFs. These results indicate that PGE2-induced VEGF production is mediated, at least partially, through cAMP-dependent signaling pathways. Therapies targeting the EP4 receptor may be effective in inhibiting the development of nasal polyps.

Keyword

Nasal polyp; fibroblast; prostaglandin E2; vascular endothelial growth factor; E-prostanoid receptor; cyclic adenosine monophosphate
Full Text Links
  • AAIR
Share
  • Twitter
  • Facebook
Copyright © 2020 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr