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

Background-Nitric oxide (NO) and prostanoids are mediators of vascular and bronchial tone that are postulated to be involved in asthma. increased leve ls of both are found in asthmatic subjects and are synthesised by enzymes t hat have cytokine inducible forms: inducible NO synthase (iNOS) and cyclo-o xygenase-2 (COX-2), respectively. We hypothesised that the in vivo expressi on 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 co rticosteroid treatment. Methods-Bronchial biopsy specimens were obtained from three groups of subje cts: atopic asthmatics treated with p, agonists alone (n=7), atopic asthmat ics additionally receiving regular treatment with corticosteroids (n=8), an d nonasthmatic control subjects (n=10). Expression of iNOS and COX-2 mRNA a nd immunoreactive protein was studied using in situ hybridisation and quant itative immunohistochemistry. Results-Immunoreactivity and the hybridisation signal for iNOS and COX-2 we re mainly localised in the airway epithelium. The proportion of epithelium immunostained was significantly greater in the non-steroid treated asthmati c subjects (iNOS 8.6 (1.8)%; COX-2 26.3 (4.6)%) than either the steroid tre ated 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-steroi d treated group of asthmatic subjects than in the other two groups. Conclusions-These findings highlight the potential role of the airway epith elium both as a contributor to the inflammatory process in asthma and as a target for inhaled corticosteroid treatment in this disease.