Reduced expression of COXs and production of prostaglandin E2 in patients with nasal polyps with or without aspirin-intolerant asthma

Abstract

Researchers have debated whether regulation of the COX enzymes (COX-1 and COX-2), which mediate production of prostaglandins (PGs), affects the pathogenesis of nasal polyps (NPs) and aspirin-intolerant asthma (AIA). We investigated the roles of PGE(2), COX-1 and COX-2, and PGE(2) receptors in the development of NPs and AIA by measuring their expression in fibroblasts derived from nasal mucosa (NM) and NPs. Fibroblasts were isolated from the NM of subjects without asthma who had septal deviation, turbinate hypertrophy, or both (control subjects, n= 7); NPs of aspirin-tolerant nonasthmatic patients (n= 7); and NPs of patients with asthma who were intolerant of aspirin (n= 7). Polyp samples were collected during endoscopic surgery. Cultures were stimulated with IL-1β (10 ng/mL) for 72 hours. We used ELISA, immunoblotting, and immunofluorescence analyses to measure secretion of PGE(2), expression of COX-1 and COX-2, and expression of the PGE(2) receptors EP1 to EP4. Compared with NM from control subjects, PGE(2) concentrations were significantly lower in IL-1β-stimulated fibroblasts from patients with NPs who were tolerant to aspirin and even lower in polyps from patients with AIA. Similarly, IL-1β exposure induced the expression of COX-1 and COX-2 in fibroblasts from NM of control subjects, had only moderate effects on fibroblasts from NPs of aspirin-tolerant nonasthmatic patients, and almost no effect on fibroblasts from NPs of patients with AIA. IL-1β also induced expression of EP2 in fibroblasts from control NM but not in fibroblasts from NPs of aspirin-tolerant nonasthmatic patients or those with AIA. Alterations in the COX pathway (ie, reduced production of PGE(2) and lack of upregulation of COX-1, COX-2, and EP2 under conditions of inflammation) are associated with NPs in patients with or without AIA.