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Cyclooxygenase-2 mRNA Is Downexpressed in Nasal Polyps from Aspirin-sensitive Asthmatics

1999; American Thoracic Society; Volume: 160; Issue: 1 Linguagem: Inglês

10.1164/ajrccm.160.1.9808048

1535-4970

César Picado, Julia Fernández-Morata, Manel Juan, Jordi Roca‐Ferrer, Mireya Fuentes, Antoni Xaubet, Joaquim Mullol,

Drug-Induced Adverse Reactions

Exogenous prostaglandin E2 (PGE2) given by inhalation almost completely abrogates aspirin-induced asthma and the accompanying increase in cysteinyl-leukotrienes production. Cyclooxygenase (COX) may be present in cells in both constitutive (COX-1) and inducible (COX-2) forms. To increase the production of the potentially protective endogenous PGE2, COX-2 should be upregulated. We hypothesize that an abnormal regulation of COX-2 will predispose patients with asthma to develop aspirin-intolerant asthma/rhinitis (AIAR). We therefore examined the expression of COX-2 messenger RNA (mRNA) in healthy nasal mucosa (n = 11) and in nasal polyps from both patients with AIAR (n = 8) and those with aspirin-tolerant asthma/rhinitis (ATAR) (n = 20). After total mRNA extraction, COX-1 and COX-2 mRNA expression were measured using a reverse transcriptase (RT)-semiquantitative PCR technique. Hybrid primers of COX-1 · glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or COX-2 · GAPDH were used to create PCR products that were cloned and used as internal standard controls in the competitive PCR reaction. Results are presented as mean ± standard error of 106 molecules of mRNA/ μ g of total RNA. No differences in COX-1 mRNA expression were found between nasal mucosa and nasal polyps from both patients with ATAR and those with AIAR. However, COX-2 mRNA expression in nasal polyps from the AIAR group (0.38 ± 0.10) was markedly and significantly lower than in polyps from the ATAR group (2.93 ± 0.52, sevenfold, p < 0.0001) and nasal mucosa (2.10 ± 0.54, sixfold, p < 0.01). These findings suggest that an inadequate COX-2 regulation may be involved in AIAR.