Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts

Abstract

Background: Vascular endothelial growth factor (VEGF) is known to be associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). VEGF is produced by a variety of cells including fibroblasts. It was recently reported that prostaglandin (PG) E2 induces VEGF release by nasal polyp fi- broblasts. However, little is known regarding possible regulation of VEGF by other PGs. We have reported that molecules that regulate PGD2 metabolism play roles in the pathogenesis of CRS including in local eosinophilia and type 2 cytokine production. In the present study, we sought to determine whether PGD2 regulates VEGF release by nasal polyp fibroblasts. Methods: Nasal polyp fibroblasts were established from nasal polyps. These fibroblasts were stimulated with serial dilutions of PGD2 or PGD2 receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. The concentration of VEGF in the culture supernatants was determined using ELISA. Results: 5 mM of PGD2 significantly induced VEGF release by nasal polyp fibroblasts. VEGF release was also obtained by stimulation with a DP receptor-selective, but not with a CRTH2 receptor-selective agonist. In addition, PGD2-induced VEGF release was significantly inhibited by pre-treatment with DP receptor-selective antagonists. In contrast, pre-treatment with a CRTH2 receptor-selective antagonist significantly enhanced PGD2-induced VEGF release. Conclusions: PGD2 stimulates VEGF production via DP but not CRTH2 receptors in nasal polyp fibroblasts.