Altered Inhibitory Function of the E-Type Prostanoid Receptor 4 in Eosinophils and Monocytes from Aspirin-Intolerant Patients

作者：Luschnig Petra; Frei Robert; Lang Loidolt Doris; Rozsasi Ajnacska; Tomazic Peter V; Lippe Irmgard T; Schuligoi Rufina^*; Heinemann Akos

来源：Pharmacology, 2014, 94(5-6): 280-286.

DOI：10.1159/000369827

• Aspirin-exacerbated respiratory disease
• E-type prostanoid receptor 4
• Eosinophils
• Monocytes
• Prostaglandin E-2
• Tumor necrosis factor-alpha

Prostaglandin (PG) E-2 has been implicated in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). Etype 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 PGE(2) 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 PGE(2) 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 PGE(2) synthesis, but the response to EP4 receptor activation with respect to inhibition of LPS-induced tumor necrosis factor-a 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.

• 出版日期2014