Acute Respiratory Barrier Disruption by Ozone Exposure in Mice

Sokołowska, Milena; Quesniaux, Valérie; Akdiş, Cezmi A.; Chung, Kian Fan; Ryffel, Bernhard; Togbé, Dieudonnée

doi:10.3389/fimmu.2019.02169

Cited by 64 publications

(56 citation statements)

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“…The acute respiratory barrier disruption by ozone has been recently reviewed in an accompanying review in this series ( 65 ). This first phase is followed by a robust barrier injury with cell death, protein leak, and influx of ROS expressing myeloid cells including neutrophils, IL-1α and IL-33 production by epithelial and myeloid cells within 6–12 h. Thus, a biphasic response is observed, an immediate direct membrane damage by ROS and a second phase mediated by myeloid cells, which aggravates the damage of the epithelium and inflammation.…”

Section: Mechanisms Of Ozone-induced Oxidative Stress On Inflammationmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Mechanisms Of Ozone-induced Oxidative Stress On Inflammationmentioning

confidence: 99%

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

et al. 2020

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“…For epithelial cells, ROS disrupts the TJ directly by protein modifications such as thiol oxidation, phosphorylation, nitration, and carbonylation. Multiple inflammatory pathways may also be stimulated to impair the TJ and barrier function [ 14 , 30 , 31 ]. The known ROS-producing enzymes in mammalian cells are NADPH oxidases, xanthine oxidase, lipoxygenases, and cytochrome P450 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…low concentration, p-SPAK phosphorylated-SPAK. Data are expressed as the mean ± SD pathways may also be stimulated to impair the TJ and barrier function [14,30,31]. The known ROS-producing enzymes in mammalian cells are NADPH oxidases, xanthine oxidase, lipoxygenases, and cytochrome P450 [32].…”

Section: Discussionmentioning

confidence: 99%

SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure

Shen

Lin

et al. 2021

BMC Pulm Med

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Background Hyperoxia downregulates the tight junction (TJ) proteins of the alveolar epithelium and leads to barrier dysfunction. Previous study has showed that STE20/SPS1-related proline/alanine-rich kinase (SPAK) interferes with the intestinal barrier function in mice. The aim of the present study is to explore the association between SPAK and barrier function in the alveolar epithelium after hyperoxic exposure. Methods Hyperoxic acute lung injury (HALI) was induced by exposing mice to > 99% oxygen for 64 h. The mice were randomly allotted into four groups comprising two control groups and two hyperoxic groups with and without SPAK knockout. Mouse alveolar MLE-12 cells were cultured in control and hyperoxic conditions with or without SPAK knockdown. Transepithelial electric resistance and transwell monolayer permeability were measured for each group. In-cell western assay was used to screen the possible mechanism of p-SPAK being induced by hyperoxia. Results Compared with the control group, SPAK knockout mice had a lower protein level in the bronchoalveolar lavage fluid in HALI, which was correlated with a lower extent of TJ disruption according to transmission electron microscopy. Hyperoxia down-regulated claudin-18 in the alveolar epithelium, which was alleviated in SPAK knockout mice. In MLE-12 cells, hyperoxia up-regulated phosphorylated-SPAK by reactive oxygen species (ROS), which was inhibited by indomethacin. Compared with the control group, SPAK knockdown MLE-12 cells had higher transepithelial electrical resistance and lower transwell monolayer permeability after hyperoxic exposure. The expression of claudin-18 was suppressed by hyperoxia, and down-regulation of SPAK restored the expression of claudin-18. The process of SPAK suppressing the expression of claudin-18 and impairing the barrier function was mediated by p38 mitogen-activated protein kinase (MAPK). Conclusions Hyperoxia up-regulates the SPAK-p38 MAPK signal pathway by ROS, which disrupts the TJ of the alveolar epithelium by suppressing the expression of claudin-18. The down-regulation of SPAK attenuates this process and protects the alveolar epithelium against the barrier dysfunction induced by hyperoxia.

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“…100 Recently, it was reported in mice that IL-33 mediates ozone-induced inflammation, induces the expression of TJ and AJ proteins (claudin-3, ZO-1, E-cadherin), reduces neutrophil influx, and therefore plays an important role in the homeostasis of airway epithelial barrier. 100,101 With chronic ozone exposure, the total collagen count in the lung increases, remodeling is induced, pulmonary resistance increases, epithelial thickness decreases, and emphysema occurs. 99 Acute ozone exposure impairs epithelial barrier function and causes airway inflammation, peribronchial collagen deposition, and airway hyperresponsiveness.…”

Section: Ozonementioning

confidence: 99%

“…Epidemiological data show that chronic ozone exposure increases the mortality and morbidity of chronic respiratory diseases such as chronic obstructive pulmonary disease and asthma as a result of chronic inflammation, fibrosis, and respiratory failure. In addition, it is known to be an important trigger for severe asthma exacerbations 99,101,102 Considering the studies related to environmental ozone exposure, several short-term studies are available, but long-term ozone exposure studies are necessary to reveal the long-term effects of ozone on human respiratory epithelium.…”

Section: Ozonementioning

confidence: 99%

Environmental factors in epithelial barrier dysfunction

Sözener

Cevhertas

Nadeau

et al. 2020

Journal of Allergy and Clinical Immunology

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133

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The main interfaces controlling and attempting to homeostatically balance communications between the host and the environment are the epithelial barriers of the skin, gastrointestinal system, and airways. The epithelial barrier constitutes the first line of physical, chemical, and immunologic defenses and provides a protective wall against environmental factors. Following the industrial revolution in the 19th century, urbanization and socioeconomic development have led to an increase in energy consumption, and waste discharge, leading to increased exposure to air pollution and chemical hazards. Particularly after the 1960s, biological and chemical insults from the surrounding environment-the exposome-have been disrupting the physical integrity of the barrier by degrading the intercellular barrier proteins at tight and adherens junctions, triggering epithelial alarmin cytokine responses such as IL-25, IL-33, and thymic stromal lymphopoietin, and increasing the epithelial barrier permeability. A typical type 2 immune response develops in affected organs in asthma, rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, and atopic dermatitis. The aim of this article was to discuss the effects of environmental factors such as protease enzymes of allergens, detergents, tobacco, ozone, particulate matter, diesel exhaust, nanoparticles, and microplastic on the integrity of the epithelial barriers in the context of epithelial barrier hypothesis.

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Acute Respiratory Barrier Disruption by Ozone Exposure in Mice

Cited by 64 publications

References 100 publications

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

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

SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure

Environmental factors in epithelial barrier dysfunction

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