Nitric oxide, iNOS, and inflammation in cystic fibrosis

Nitric oxide (NO) is produced from three isoforms of nitric oxide synthase (NOS), neuronal (nNOS), endothelial (eNOS) and inducible (iNOS). Cystic fibrosis (CF) patients have an increased bacterial load in the airways which stimulates iNOS and therefore NO production. Upregulation of iNOS in normal epithelial cells protects the lung from damage, but in CF cells, iNOS is not upregulated and NO production is reduced. Reduced iNOS expression is associated with neutrophil sequestration in the lung, thus increasing the potential damage from neutrophil proteases and reactive oxygen species. In contrast, high concentrations of NO may augment the inflammatory process in acute lung injury from sepsis. Meng et al. have shown that cystic fibrosis epithelial cells, when stimulated by a cytokine mix and co-cultured with activated neutrophils, have reduced iNOS expression compared to normal epithelial cells. Although iNOS expression may not accurately reflect activity and NO production may arise from elsewhere, this study suggests that reduced iNOS expression may play a part in the pathophysiological processes in cystic fibrosis.