Nitric Oxide in Airway Inflammation

This chapter describes the localization and synthesis of nitric oxide (NO) in airways, pathophysiological roles of NO in lung diseases, signaling pathways of NO in airways, and interaction between NO and reactive oxygen species in the lung, focusing on NO as a new molecular therapeutic target in airway inflammation. NO is a diffusible, short-lived, highly reactive gaseous molecule produced from L-arginine by the NO synthase family. Biological effects of NO are mediated through the reaction of NO with a number of targets such as heme groups, cysteine residues, and iron and zinc clusters. NO is a critical player in the development of various airway inflammatory diseases and is a part of complex signaling systems associated with airway inflammatory diseases. Although the role of NO in biological processes is so complex, bidirectional, and still somewhat controversial, the interrelationship between NO and various signaling networks, as well as oxidative stress involved in airway inflammation and remodeling, has made NO more attractive for therapeutic strategy in airway inflammatory diseases. Hence, NO has a very wide range of roles in various biological systems. Although NO is known to have protective effects—antimicrobial, antiinflammatory, and antioxidative—against the pathogenesis of various disease states, there is increasing evidence regarding the deleterious impact of NO in a number of respiratory disorders including airway inflammatory diseases. Recent studies have introduced NO as a key reactive signaling molecule, suggesting that NO is located at the switching point of various molecular signals in the respiratory system.