title: Cyclooxygenase-2 mRNA is downexpressed in nasal polyps from aspirin-sensitive asthmatics.
abstract: 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 10(6) molecules of mRNA/micrograms 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.
authors.affiliation: Servei de Pneumologia i Al.lèrgia Respiratòria, Hospital Clínic, Departament de Medicina, Universitat de Barcelona, Spain. cpicado@medicina.ub.es
authors.forename: C
authors.initials: C
authors.lastname: Picado
authors.forename: J C
authors.initials: JC
authors.lastname: Fernandez-Morata
authors.forename: M
authors.initials: M
authors.lastname: Juan
authors.forename: J
authors.initials: J
authors.lastname: Roca-Ferrer
authors.forename: M
authors.initials: M
authors.lastname: Fuentes
authors.forename: A
authors.initials: A
authors.lastname: Xaubet
authors.forename: J
authors.initials: J
authors.lastname: Mullol
mesh_terms: D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015536:Down-Regulation / Q000235:genetics; D004342:Drug Hypersensitivity / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009297:Nasal Mucosa / Q000473:pathology; D009298:Nasal Polyps / Q000235:genetics*; D009669:Nose Neoplasms / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin