Upregulation of COX-1 and COX-2 in nasal polyps in cystic fibrosis

Abstract

Background: Since abnormalities in prostanoid metabolism occur in the lower airway of patients with cystic fibrosis (CF), it is likely that they could also be detected in the nose. Methods: The degree of mRNA and protein expression of cyclo-oxygenase (COX) enzymes 1 (COX-1) and 2 (COX-2) was examined using quantitative reverse competitive polymerase chain reaction (RT-PCR) and Western blot analysis in the nasal polyps from 10 patients with CF, nasal polyps from 10 non-CF patients and 11 nasal mucosa specimens. The results are presented as 10 6 cDNA molecules/mg total RNA and the densitometric ratio between protein and b-actin. Results: COX-1 mRNA levels were significantly higher in CF nasal polyps (median 2.34, 25-75th percentiles 1.6-3.2) than in the nasal mucosa (0.78, 0.11-1.21), while there was no difference with non-CF nasal polyps (1.11, 0.80-3.15). COX-1 protein levels were significantly higher in CF nasal polyps (3.63, 2.71-4.27) than in nasal mucosa (1.55, 0.66-2.33) and non-CF nasal polyps (2.19, 1.72-3.68). COX-2 mRNA was significantly higher in CF nasal polyps (3.34, 2.42-7.05) than in nasal mucosa (1.69, 0.19-3.50). No differences were found in COX-2 mRNA expression between CF and non-CF polyps (1.38, 0.12-6.07). COX-2 protein levels were also significantly higher in CF nasal polyps (0.23, 0.04-0.34) than in non-CF nasal polyps (0.011, 0.009-0.016) or nasal mucosa (0.014, 0.014-0.016). Conclusions: Upregulation in the expression of COX-1 and COX-2 could explain the high production of prostanoids reported in CF. These findings raise questions regarding the potential use of selective or nonselective COX-2 non-steroidal anti-inflammatory treatment in CF.

Fatty Acid Composition of Cultured Fibroblasts Derived from Healthy Nasal Mucosa and Nasal Polyps

“…After performing nasal tissue biopsies, Freedman et al [23] reported significantly higher levels of AA in cystic fibrosis and asthma patients compared with healthy control subjects. Interestingly, Roca-Ferrer et al [9] also found that COX-2 mRNA and protein were markedly up-regulated in NP from cystic fibrosis patients; these findings contrast with the lack of expression of COX-2 mRNA and COX-2 protein in NP from asthma patients. As expected, in cystic fibrosis the increased release of AA, together with the up-regulated COX-2, results in an enhanced production of PGE 2 , as has been demonstrated in saliva, exhaled air and urine [24][25][26].…”

“…In patients with asthma, and especially in AIA, various data support the existence of an altered regulation of the COX pathway [9][10][11][12][13][14][15]. PGE 2 levels have been reported to be low in the nasal polyps of asthma patients, as well as in nasal-polyp and bronchial fibroblasts from asthmatic patients, particularly those with aspirin sensitivity [11,[13][14][15].…”

“…As PGE 2 production mostly depends on the level of COX-2 induction under conditions of inflammation, it should be expected that the low production of PGE 2 detected in asthma and nasal polyps would be accompanied by a similar, concomitant alteration in the expression of COX-2. Accordingly, lack of up-regulation of COX-2 in the nasal polyps of asthma patients, both with and without aspirin sensitivity, has been reported in various studies [9][10][11][12]15].…”

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

“…Although understanding of the roles of COX-2 and its mediators in microbial host defense mechanisms is expanding, there are yet relatively few reports pertaining to its significance in human diseases. Our study has important clinical implications because increased prostanoid release has been reported in patients with bronchiectasis associated with cystic fibrosis (57,58). Furthermore, some studies suggest that inhibition of COX-2 delays the progression of lung disease in patients with cystic fibrosis (59), although the mechanisms are not fully understood.…”

Current views on chronic rhinosinusitis in patients with cystic fibrosis

“…Также была изучена регуляция ЦОГ-1 и ЦОГ-2 в носовых полипах у пациентов с МВ [8]. Уровень матричной РНК и выброса белков ЦОГ-1 и ЦОГ-2 в слизистой оболочке носа у пациентов с МВ был исследован с использованием полимеразной цепной реакции в режиме реального времени.…”