title: Altered inhibitory function of the E-type prostanoid receptor 4 in eosinophils and monocytes from aspirin-intolerant patients.
abstract: Prostaglandin (PG) E2 has been implicated in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). E-type prostanoid (EP) receptor 4 is known to confer inhibitory signals to eosinophils and monocytes, amongst others. In this study, we investigated whether the responsiveness of eosinophils and monocytes to PGE2 and EP4 receptor activation is altered in AERD patients. While the expression of the EP4 receptor in eosinophils was unaltered in AERD patients, inhibition of eosinophil chemotaxis by PGE2 or the EP4 agonist CAY10598 was less pronounced in AERD patients as compared to healthy control subjects. In monocytes, we found no changes in basal or lipopolysaccharide (LPS)-stimulated PGE2 synthesis, but the response to EP4 receptor activation with respect to inhibition of LPS-induced tumor necrosis factor-α release was reduced in AERD patients, especially in the presence of aspirin (acetylsalicylic acid). Our data point towards a decreased sensitivity of inhibitory EP4 receptor that may play a role in AERD.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Luschnig
authors.forename: Robert
authors.initials: R
authors.lastname: Frei
authors.forename: Doris
authors.initials: D
authors.lastname: Lang-Loidolt
authors.forename: Ajnacska
authors.initials: A
authors.lastname: Rozsasi
authors.forename: Peter V
authors.initials: PV
authors.lastname: Tomazic
authors.forename: Irmgard T
authors.initials: IT
authors.lastname: Lippe
authors.forename: Rufina
authors.initials: R
authors.lastname: Schuligoi
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects* / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C000598602:CAY10598; D008070:Lipopolysaccharides; D011760:Pyrrolidinones; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D001241:Aspirin; D002118:Calcium