Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts.
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) E2induces VEGF release by nasal polyp fibroblasts. However, little is known regarding possible regulation of VEGF by other PGs. We have reported that molecules that regulate PGD2metabolism 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 PGD2regulates VEGF release by nasal polyp fibroblasts.


METHODS
Nasal polyp fibroblasts were established from nasal polyps. These fibroblasts were stimulated with serial dilutions of PGD2or PGD2receptor (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 μM of PGD2significantly 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
PGD2stimulates VEGF production via DP but not CRTH2 receptors in nasal polyp fibroblasts.
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Department Otorhinolaryngology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
Kengo
K
Kanai
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: mokano@cc.okayama-u.ac.jp.
Mitsuhiro
M
Okano
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Tazuko
T
Fujiwara
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shin
S
Kariya
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Takenori
T
Haruna
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Ryotaro
R
Omichi
Department Otorhinolaryngology, Kagawa Rosai Hospital, Marugame, Japan.
Sei-Ichiro
SI
Makihara
Department Otorhinolaryngology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
Yuji
Y
Hirata
Department Otorhinolaryngology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
Kazunori
K
Nishizaki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D012129:Respiratory Function Tests; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D042461:Vascular Endothelial Growth Factor A; D007073:Immunoglobulin E; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor
CRTH2; DP; Nasal polyp fibroblast; PGD2; VEGF