ABSTRACT
The lung is sensitive to oxidative injury triggered by reactive oxygen and nitrogen species (ROS/RNS) due to its large epithelial surface area and blood supply. These oxygen/free radicals can be generated endogenously (e.g., from mitochondrial electron transport during respiration and during activation of phagocytes) as well as exogenously (e.g., air pollutants, silica, or cigarette smoke), leading to oxidative damage/modišcation of proteins, lipids, and DNA. Epidemiological study shows that tobacco smoking accounts for 66% of cases of chronic obstructive pulmonary disease (COPD), while biomass burning and high levels of ambient air pollution are other contributing risk factors for this disease (Christiani, 2010). Increased levels of ROS/RNS have been implicated in initiating inammatory responses in the lungs through the activation of plasma membrane receptors e.g., Toll-like receptors (TLRs), kinasesIκB kinase (IKK), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC), and transcription factors e.g., nuclear factor-kappaB (NF-κB), resulting in gene expression of pro-inammatory mediators (Rahman et al., 2002; Asehnoune et al., 2004; Marwick et al., 2004; Moodie et al., 2004; Kode et al., 2006; Yang et al., 2006, 2008; Medicherla et al., 2008; Yao et al., 2008, 2010; Moretto et al., 2009). Lung inammation not only is a common characteristic, but also plays an important role in the pathogenesis of chronic pulmonary diseases, such as COPD, asthma, pulmonary šbrosis, and lung cancer (Figure 3.1). In certain conditions, these diseases can occur simultaneously and affect each other. For example, šbrosis around the small airway is a major reason for irreversible airway narrowing in patients with COPD (Hogg et al., 2004a). Moreover, COPD has been shown to increase the susceptibility for lung tumorigenesis up to 4.5-fold (Yao and Rahman, 2009). Therefore, understanding the cellular and molecular mechanisms for inammation would identify the targets in
FIGURE 3.1 Involvement of inammation in chronic lung diseases. Environmental irritants, such as tobacco smoking, biomass fuel burning, and air pollutants, cause lung inammation by generating oxidative stress and activating a variety of receptors, kinases, and transcription factors. Lung inammation not only is a common feature, but also is involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung šbrosis, and cancer.
