Inflammation and lung cancer: roles of reactive oxygen/nitrogen species.
The lung is a highly specialized organ that facilitates uptake of oxygen and release of carbon dioxide. Due to its unique structure providing enormous surface area to outside ambient air, it is vulnerable to numerous pathogens, pollutants, oxidants, gases, and toxicants that are inhaled continuously from air, which makes the lung susceptible to varying degrees of oxidative injury. To combat these unrelenting physical, chemical, and biological insults, the respiratory epithelium is covered with a thin layer of lining fluid containing several antioxidants and surfactants. Inhaled toxic agents stimulate the generation of reactive oxygen/nitrogen species (ROS/RNS), which in turn provoke inflammatory responses resulting in the release of proinflammatory cytokines and chemokines. These subsequently stimulate the influx of polymorphonuclear leukocytes (PMNs) and monocytes into the lung so as to combat the invading pathogens or toxic agents. In addition to the beneficial effects, persistent inhalation of the invading pathogens or toxic agents may result in overwhelming production of ROS/RNS, producing chronic inflammation and lung injury. During inflammation, enhanced ROS/RNS production may induce recurring DNA damage, inhibition of apoptosis, and activation of proto-oncogenes by initiating signal transduction pathways. Therefore, it is conceivable that chronic inflammation-induced production of ROS/RNS in the lung may predispose individuals to lung cancer. This review describes the complex relationship between lung inflammation and carcinogenesis, and highlights the role of ROS/RNS in cancer development.
Azad
Neelam
N
Department of Pharmaceutical and Pharmacological Sciences, West Virginia University, Morgantown, West Virginia, USA.
Rojanasakul
Yon
Y
Vallyathan
Val
V
D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D026361:Reactive Nitrogen Species / Q000378:metabolism* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000633:toxicity
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species