Expression of cyclooxygenase enzymes and prostaglandin E2 receptors in inflammatory airway diseases

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Aspirin-intolerant asthma (AIA) is a syndrome where the interplay between cyclooxygenase (COX) and lipoxygenase (LOX) pathways is evident and is characterized by several abnormalities in the regulation and biosynthesis of eicosanoid mediators and eicosanoid receptors. Several observations indicate the presence of a complex change in the arachidonic acid (AA) metabolism in patients who suffer from AIA. However, previous studies showed some discrepant results when upper and lower airways were analyzed, and there are no clear explanations for this. The inflammatory responses in upper airways are often associated with the presence of nasal polyps, structures never seen in the lower airways. In this study, upper and lower airways were compared, in order to verify if the multiple factors of the COX pathway are differentially regulated considering both respiratory tracts. To perform the experiments, fibroblasts from nasal mucosa (NM) and bronchial mucosa (BM) of non-asthmatic subjects undergoing corrective surgery and fibrobronchoscopy, respectively, (control group) were compared with NM, nasal polyp (NP), and BM fibroblasts isolated from non-asthmatic and AIA patients suffering from chronic rhinosinusitis (CRS) with NP. The data presented in this investigation suggest that in lower airways, the presence of aspirin intolerance does not seem to alter the expression of COX enzymes or the production of prostaglandin (PG) E2. Considering the expression of the EP receptors, the data suggest significant differences through fibroblasts from upper airways tissues. The differences observed between upper and lower airways combined with others verified in previous studies might contribute to the pathogenesis of nasal polyposis.