Altered expression and signalling of EP2 receptor in nasal polyps of AERD patients: role in inflammation and remodelling

Abstract

© 2016, AMC. All right reserved. 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) E 2 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 EP 1-4 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 EP 2 , EP 3 and EP 4 at baseline. Lower expression of EP 2 and higher expression of EP 4 was observed in NP-AERD compared with NM-C. Stimulation with PGE 2 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 PGE 2 and butaprost was lower in NP-AERD than in NM-C fibroblasts. Similarly, the capacity of PGE 2 and butaprost to inhibit GM-CSF release was lower in NP-AERD than in NM-C. Conclusions: The altered expression of EP 2 in AERD may contribute to reduce the capacity of PGE 2 to mediate anti-proliferative and anti-inflammatory effects.