Open AccessAltered expression and signalling of EP2 receptor in nasal polyps of AERD patients: role in inflammation and remodelling
Author(s) -
Liliana Machado-Carvalho,
Rosa Torres,
M Pérez-González,
I Alobid,
Joaquim Mullol,
Laura Pujols,
Jordi RocaFerrer,
César Picado
Publication year - 2016
Publication title -
rhinology (amsterdam. online)/rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.275
H-Index - 57
eISSN - 1996-8604
pISSN - 0300-0729
DOI - 10.4193/rhino15.207
Subject(s) - prostaglandin e2 receptor , nasal polyps , receptor , prostaglandin d2 , medicine , prostaglandin e2 , endocrinology , immunology , agonist
Background: Down-regulation of the E-prostanoid (EP)2 receptor has been reported in aspirin exacerbated respiratory disease (AERD). We aimed to evaluate the expression and activation of EP receptors in AERD and their role in prostaglandin (PG) E2 signalling. Methods: Samples were obtained from nasal mucosa of control subjects (NM-C, n=7) and from nasal polyps of AERD patients (NP-AERD, n=7). Expression of EP1-4 was assessed at baseline. Fibroblasts were stimulated with receptor agonists to measure cAMP levels, cell proliferation and granulocyte-macrophage colony-stimulating factor (GM-CSF) release. Results: NM-C and NP-AERD samples and fibroblasts expressed EP2, EP3 and EP4 at baseline. Lower expression of EP2 and higher expression of EP4 was observed in NP-AERD compared with NM-C. Stimulation with PGE2 and butaprost caused a higher increase in cAMP in NM-C than in NP-AERD. On the contrary, CAY10598 produced a higher production of cAMP in NP-AERD compared with NM-C. The anti-proliferative effect of PGE2 and butaprost was lower in NP-AERD than in NM-C fibroblasts. Similarly, the capacity of PGE2 and butaprost to inhibit GM-CSF release was lower in NP-AERD than in NM-C. Conclusions: The altered expression of EP2 in AERD may contribute to reduce the capacity of PGE2 to mediate anti-proliferative and anti-inflammatory effects.