Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment

Abstract

Background-Nitric oxide (NO) and prostanoids are mediators of vascular and bronchial tone that are postulated to be involved in asthma. Increased levels of both are found in asthmatic subjects and are synthesised by enzymes that have cytokine inducible forms: inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), respectively. We hypothesised that the in vivo expression of iNOS and COX-2 in the airways would be increased in asthma, and that these cytokine inducible enzymes may represent targets for regulation by corticosteroid treatment. Methods-Bronchial biopsy specimens were obtained from three groups of subjects: atopic asthmatics treated with 2 agonists alone (n=7), atopic asthmatics additionally receiving regular treatment with corticosteroids (n=8), and nonasthmatic control subjects (n=10). Expression of iNOS and COX-2 mRNA and immunoreactive protein was studied using in situ hybridisation and quantitative immunohistochemistry. Results-Immunoreactivity and the hybridisation signal for iNOS and COX-2 were mainly localised in the airway epithelium. The proportion of epithelium immunostained was significantly greater in the non-steroid treated asthmatic subjects (iNOS 8.6 (1.8)%; COX-2 26.3 (4.6)%) than either the steroid treated asthmatics (iNOS 3.4 (1.0)%, p=0.009; COX-2 13.0 (0.6)%, p=0.0015) or the non-asthmatic controls (iNOS 4.2 (0.9)%, p=0.018; COX-2 11.6 (0.6)%, p=0.0003). Similarly, the hybridisation signal was stronger in the non-steroid treated group of asthmatic subjects than in the other two groups. Conclusions-These findings highlight the potential role of the airway epithelium both as a contributor to the inflammatory process in asthma and as a target for inhaled corticosteroid treatment in this disease.

Comparison of online single-breath vs. online multiple-breath exhaled nitric oxide in school-age children

“…In both the clinical and the research settings, eNO aids in discriminating different asthma phenotypes, particularly the atopic vs. the nonatopic form (6,7). Increased in atopic or asthmatic patients and reduced under corticosteroid treatment, eNO has assisted with diagnosis and clinical guidance for pediatric and adult patients alike (8).…”

Up-regulation of bradykinin receptors in rat bronchia via IκB kinase-mediated inflammatory signaling pathway

“…Increased expressions of COX-2, iNOS and MMP-9 have been observed in airway inflammation (Birrell et al, 2006;Redington et al, 2001). It has been reported that recombinant human IL-6 significant leftward shifts the concentration-response curve of des-Arg 9 -bradykinin in human umbilical vein (Sardi et al, 2002); COX-2 may participate in the up-regulation of B 1 receptor-mediated contraction of the rabbit aorta (Medeiros et al, 2001); inhibition of iNOS significantly reduced the up-regulation of B 1 receptor mediated contraction in a murine colitis model (Hara et al, 2008).…”

Are emerging PGD2 antagonists a promising therapy class for treating asthma?

“…Both COX-2 [7] and hematopoietic PGDS [8] are more highly expressed in asthmatic lungs, suggesting a greater capacity for producing PGD 2 , and there are greater numbers of CRTH2 + cells [9], increasing sensitivity to PGD 2 . These observations are more pronounced in patients with poor asthma control [8].…”