Figure 8. NOX activation, signaling and lung disease phenotypes.

Damaging stimuli, such as microbes, cigarette smoking and pollution activate distinct NOXs beyond their physiological signaling and stimulate their participation in the development of various lung diseases including lung injury, fibrosis, COPD and asthma. NOX2 is reportedly fundamental to the activation of ENaC channels and alveolar fluid clearance by epithelial cells and thus is deemed homeostatic in the lung. On the other hand, NOX2 can effect lung injury via NFκB-mediated pathways. Lung fibrosis is under the effect of NOX4 expression. COPD involves the participation of NOX1, NOX2 and NOX4 and part of that pathology is mediated via the suppression of SIRT1 and disinhibition of MMP9. Asthma is brought about by NOX2, NOX4 and DUOX1 through a variety of factors including CK2α-mediated NFκB as well as, in the case of DUOX, EGFR and activation of pro-inflammatory cytokines. While NOX5 has been correlated with a number of these disorders, no studies to date appear to have demonstrated causality in in vitro or in vivo models. COPD: Chronic obstructive pulmonary disease; CK2 α: casein kinase 2α; SIRT1: member of the sirtuin family; MMP9: Matrix Metalloproteinase 9; EGFR: epidermal growth factor.