Cyclooxygenase-2 mRNA is downexpressed in nasal polyps from aspirin-sensitive asthmatics

Exogenous prostaglandin E-2 (PGE(2)) 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 b oth constitutive (COX-1) and inducible (COX-2) forms. To increase the produ ction of the potentially protective endogenous PGE(2), COX-2 should be upre gulated. We hypothesize that an abnormal regulation of COX-2 will predispos e patients with asthma to develop aspirin-intolerant asthma/rhinitis (AIAR) . We therefore examined the expression of COX-2 messenger RNA (mRNA) in hea lthy 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). A fter total mRNA extraction, COX-1 and COX-2 mRNA expression were measured u sing a reverse transcriptase (RT)-semiquantitative PCR technique. Hybrid pr imers of COX-1.glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or COX-2.GA PDH 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/mu g of total RNA. No dif ferences 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 mR NA expression in nasal polyps from the AIAR group (0.38 +/- 0.10) was marke dly 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 invo lved in AIAR.