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Cyclooxygenase 1 and cyclooxygenase 2 expression is abnormally regulated in human nasal polyps
Authors:Mullol Joaquim  Fernàndez-Morata Joan C  Roca-Ferrer Jordi  Pujols Laura  Xaubet Antoni  Benitez Pedro  Picado Cesar
Affiliation:Institut d'Investigacions Biomèdiques August Pi I Sunyer, Institut Clínic de Pneumologia I Cirurgia Toràcica, Hospital Clínic, Barcelona, Spain.
Abstract:BACKGROUND: There is evidence that impairment of prostanoid metabolism might be involved in the pathogenesis of nasal polyps (NPs). Prostanoids are synthesized by 2 cyclooxygenase (Cox) enzymes, one constitutive (Cox-1) and another inducible (Cox-2). OBJECTIVE: The aim of these studies was to investigate Cox-1 and Cox-2 regulation in NPs of aspirin-tolerant human patients compared with that seen in nasal mucosa (NM). METHODS: Cultured explants from human NPs and healthy mucosa from patients undergoing polypectomy and corrective nasal surgery, respectively, were examined for Cox-1 and Cox-2 expression by means of semiquantitative competitive PCR and Western blotting. RESULTS: Cox-1 mRNA was spontaneously upregulated in cultured NM but not in NPs. A spontaneous but delayed upregulation of Cox-2 mRNA was found in NPs (24 hours) compared with that seen in NM (6 hours). After cytokine stimulation (IFN-gamma, IL-1beta, and TNF-alpha), the induction of Cox-2 mRNA and protein was also faster in NM (1 hour) than in NPs (4 hours). CONCLUSION: These data showing an abnormal regulation of Cox-1 and Cox-2 in NPs from aspirin-tolerant patients reinforce the concept that prostanoid metabolism might be important in the pathogenesis of inflammatory nasal diseases and suggest a potential role for this alteration in the formation of NPs.
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