Am. J. Respir. Crit. Care Med., Volume 160, Number 1, July 1999, 291-296

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

CÉSAR PICADO, JOAN C. FERNANDEZ-MORATA, MANEL JUAN, JORDI ROCA-FERRER, MIREIA FUENTES, ANTONI XAUBET, and JOAQUIM MULLOL

Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic, Departament de Medicina, Universitat de Barcelona; Institut d'Investigacions Biomèdiques August Pi i Sunyer; Unitat d'Immunologia, Hospital Germans Trias i Pujol de Badalona, Barcelona, Spain

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/µg 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.

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