Effect of prostaglandin E2 on vascular endothelial growth factor production in nasal polyp fibroblasts

Dong Yeol Han, Jung Sun Cho, You Mi Moon, Hye Rim Lee, Heung Man Lee, Byung Don Lee, Byoung Joon Baek

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)224-231
Number of pages8
JournalAllergy, Asthma and Immunology Research
Volume5
Issue number4
DOIs
Publication statusPublished - 2013 Aug 15

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Keywords

  • Cyclic adenosine monophosphate
  • E-prostanoid receptor
  • Fibroblast
  • Nasal polyp
  • Prostaglandin E2
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

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