title: Altered expression and signalling of EP2 receptor in nasal polyps of AERD patients: role in inflammation and remodelling.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  The altered expression of EP2 in AERD may contribute to reduce the capacity of PGE2 to mediate anti-proliferative and anti-inflammatory effects.
authors.affiliation: Clinical and Experimental Respiratory Immunoallergy, Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Machado-Carvalho
authors.affiliation: Centro de Investigaciones Biomedicas en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Torres
authors.affiliation: Clinical and Experimental Respiratory Immunoallergy, Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Perez-Gonzalez
authors.affiliation: Clinical and Experimental Respiratory Immunoallergy, Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Alobid
authors.affiliation: Clinical and Experimental Respiratory Immunoallergy, Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Mullol
authors.affiliation: Clinical and Experimental Respiratory Immunoallergy, Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Pujols
authors.affiliation: Clinical and Experimental Respiratory Immunoallergy, Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Roca-Ferrer
authors.affiliation: Clinical and Experimental Respiratory Immunoallergy, Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Picado
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D012140:Respiratory Tract Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018078:Receptors, Prostaglandin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000242:Cyclic AMP; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone; D001241:Aspirin