Oxidative Stress in Ozone-Induced Chronic Lung Inflammation and Emphysema: A Facet of Chronic Obstructive Pulmonary Disease

Abstract

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke and characterized by chronic inflammation, alveolar destruction (emphysema) and bronchiolar obstruction. Ozone is a gaseous constituent of urban air pollution resulting from photochemical interaction of air pollutants such as nitrogen oxide and organic compounds. While acute exposure to ozone induces airway hyperreactivity and neutrophilic inflammation, chronic ozone exposure in mice causes activation of oxidative pathways resulting in cell death and a chronic bronchial inflammation with emphysema, mimicking cigarette smoke-induced COPD. Therefore, the chronic exposure to ozone has become a model for studying COPD. We review recent data on mechanisms of ozone induced lung disease focusing on pathways causing chronic respiratory epithelial cell injury, cell death, alveolar destruction, and tissue remodeling associated with the development of chronic inflammation and AHR. The initial oxidant insult may result from direct effects on the integrity of membranes and organelles of exposed epithelial cells in the airways causing a stress response with the release of mitochondrial reactive oxygen species (ROS), DNA, and proteases. Mitochondrial ROS and mitochondrial DNA activate NLRP3 inflammasome and the DNA sensors cGAS and STING accelerating cell death pathways including caspases with inflammation enhancing alveolar septa destruction, remodeling, and fibrosis. Inhibitors of mitochondrial ROS, NLRP3 inflammasome, DNA sensor, cell death pathways, and IL-1 represent novel therapeutic targets for chronic airways diseases underlined by oxidative stress.

Regulation of Lysosome-Associated Membrane Protein 3 (LAMP3) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling

“…Protein interaction network analysis involved in redox regulation revealed that heme oxygenase 1 or HMOX1 plays a major role with connections to SOD3 and ferritin heavy chain 1 (FTH1) of antioxidant network and LCN2, 5' aminolevulinate synthase 1 (ALAS1), and STAT3 of lipid metabolism network (Figure 13C). Consistent with these results reactive oxygen species and oxidative stress have been implicated in modulating lung type II cell metabolism and lung diseases (57,59,60).…”

Bibliometric Analysis of the Inflammasome and Pyroptosis in Brain

“…In severe fever with thrombocytopenia syndrome (SFTS) virus infection, the cytosolic mtDNA binds and triggers NLRP3 inflammasome activation resulting in SFTS disease progression and fatal outcome ( Li et al, 2020 ). The mtROS/inflammasome pathway involves arsenic-induced hepatic insulin resistance ( Jia et al, 2020 ) and ozone-induced chronic lung inflammation and emphysema ( Wiegman et al, 2020 ). Researches demonstrate that rapamycin reduces NLRP3 inflammasome activation by inhibiting the mTOR/NF-κB pathway in macrophages ( Dai et al, 2019 ), and mTOR regulates NLRP3 inflammasome activation via reactive oxygen species in murine lupus ( Li et al, 2018 ).…”

Ozone-Induced Oxidative Stress, Neutrophilic Airway Inflammation, and Glucocorticoid Resistance in Asthma

“…O 3 exposure results in accumulation of reactive oxygen species (ROS) most likely through lipid peroxidation processes of the pulmonary surfactant phospholipids (60) and cell membranes (126)(127)(128). ROS in turn rapidly activate the release of alarmins IL-1b, IL-6, IL-23, IL-33, TNF-a, and TSLP (Figure 1A) leading to a cascade of proinflammatory changes in structural and immune cells in the respiratory mucosal tissue (106,116,122,129,(131)(132)(133)(134)(135)(136). Activation of the RORgt proinflammatory signaling pathway leads to mRNA transcription of the IL-17A and IL-22 genes (Figure 1B) (131,(137)(138)(139)(140)(141)(142)(143)(144)(145)(146).…”

“…Amongst the environmental causes our review is focused on inhalational exposure to the toxic air pollutant, ozone (O 3 ) as it was found to be a significant contributor to respiratory illness. Specifically, O 3 induces airway hyperreactivity in mouse models of asthma (6,86,87,89,91,(98)(99)(100)(101)(102)(103)(104)(105)(106)(107), in Th2 low asthma in rhesus macaques (94,108) and in healthy human subjects and patients with asthma and COPD (6,7,59,(109)(110)(111)(112)(113)(114)(115)(116). Ground-level (tropospheric) O 3 is generated by the action of sunlight's UV rays from precursors (mostly air pollutants containing hydrocarbons, volatile organic compounds [VOC] and nitrogen oxides emitted during fossil fuel combustion).…”