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

作者：Machado Carvalho Liliana^*; Torres Rosa; Perez Gonzalez Maria; Alobid Isam; Mullol Joaquim; Pujols Laura; Roca Ferrer Jordi; Picado Cesar

来源：Rhinology, 2016, 54(3): 254-265.

DOI：10.4193/Rhino15.207

• aspirin-exacerbated respiratory disease
• fibroblasts
• nasal polyp
• prostaglandin E-2
• prostaglandin E-2 receptors

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 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 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 EP2 in AERD may contribute to reduce the capacity of PGE(2) to mediate anti-proliferative and anti-inflammatory effects.

• 出版日期2016-9