Impact of ozone on claudins and tight junctions in the lungs

Kim, Byeong-Gon; Lee, Pureun‐Haneul; Lee, Sun-Hye; Park, Choon-Sik; Jang, An‐Soo

doi:10.1002/tox.22566

Cited by 37 publications

(31 citation statements)

References 43 publications

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“…More interestingly, previous studies by Reddy et al (2016) on BVES suggests an enhancing and suppressive effect on Notch and Wnt pathways respectively in BVES -/- mice. An interesting study by Kim et al (2018) on the exposure of ozone and TJ proteins turned out to be revealing us another tie up between TJ proteins and signaling pathways, the immune signaling networks. They examined primary human lung epithelial cells and mouse models to understand the relationship of TJ proteins in exposure to ozone conditions.…”

Section: Cross-talk Of Claudins With Signaling Pathways In Cancermentioning

confidence: 99%

Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk

et al. 2019

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The ability of epithelial cells to organize through cell–cell adhesion into a functioning epithelium serves the purpose of a tight epithelial protective barrier. Contacts between adjacent cells are made up of tight junctions (TJ), adherens junctions (AJ), and desmosomes with unique cellular functions and a complex molecular composition. These proteins mediate firm mechanical stability, serves as a gatekeeper for the paracellular pathway, and helps in preserving tissue homeostasis. TJ proteins are involved in maintaining cell polarity, in establishing organ-specific apical domains and also in recruiting signaling proteins involved in the regulation of various important cellular functions including proliferation, differentiation, and migration. As a vital component of the epithelial barrier, TJs are under a constant threat from proinflammatory mediators, pathogenic viruses and bacteria, aiding inflammation and the development of disease. Inflammatory bowel disease (IBD) patients reveal loss of TJ barrier function, increased levels of proinflammatory cytokines, and immune dysregulation; yet, the relationship between these events is partly understood. Although TJ barrier defects are inadequate to cause experimental IBD, mucosal immune activation is changed in response to augmented epithelial permeability. Thus, the current studies suggest that altered barrier function may predispose or increase disease progression and therapies targeted to specifically restore the barrier function may provide a substitute or supplement to immunologic-based therapies. This review provides a brief introduction about the TJs, AJs, structure and function of TJ proteins. The link between TJ proteins and key signaling pathways in cell proliferation, transformation, and metastasis is discussed thoroughly. We also discuss the compromised intestinal TJ integrity under inflammatory conditions, and the signaling mechanisms involved that bridge inflammation and cancer.

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Section: Cross-talk Of Claudins With Signaling Pathways In Cancermentioning

confidence: 99%

Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk

et al. 2019

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“…These effects might be the result of ozone exposure induced changes in the expression of claudin (CLDN) proteins which are protein components of tight junctions. In mice exposed to ozone an increased expression levels of CLDN3 and CLDN4 while a reduction in CLDN14 was reported ( 59 ). These workers also showed that bronchial epithelial cell integrity was disrupted and that the trans-electrical resistance between cells was decreased leading to cell disintegration.…”

Section: Mechanisms Of Ozone-induced Oxidative Stress On Inflammationmentioning

confidence: 99%

“…These workers also showed that bronchial epithelial cell integrity was disrupted and that the trans-electrical resistance between cells was decreased leading to cell disintegration. These changes were associated with elevated ROS and increased expression of antioxidant defense system involving Nrf2 and Keap1 ( 59 ). Another potential mechanism is lipid peroxidation, which is induced by ozone in human alveolar epithelial cells ( 60 ) and in lung surfactant ( 61 ).…”

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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“…Ozone also affects epithelial cell tight junctions in vivo by suppressing the expression of claudins (CLDNs) (103). Chronic ozone exposure increased CLDN3, CLDN4, ROS, Nrf2, and Keap1 protein expression but decreased lung CLDN14 protein expression.…”

Section: Effect Of Ozone On Gene Expression In Animal and Cellular Momentioning

confidence: 99%

Transcriptional Effects of Ozone and Impact on Airway Inflammation

2019

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Epidemiological and challenge studies in healthy subjects and in individuals with asthma highlight the health impact of environmental ozone even at levels considered safe. Acute ozone exposure in man results in sputum neutrophilia in 30% of subjects particularly young children, females, and those with ongoing cardiopulmonary disease. This may be associated with systemic inflammation although not in all cases. Chronic exposure amplifies these effects and can result in the formation of asthma-like symptoms and immunopathology. Asthmatic patients who respond to ozone (responders) induce a greater number of genes in bronchoalveolar (BAL) macrophages than healthy responders with up-regulation of inflammatory and immune pathways under the control of cytokines and chemokines and the enhanced expression of remodeling and repair programmes including those associated with protease imbalances and cell-cell adhesion. These pathways are under the control of several key transcription regulatory factors including nuclear factor (NF)-κB, anti-oxidant factors such as nuclear factor (erythroid-derived 2)-like 2 NRF2, the p38 mitogen activated protein kinase (MAPK), and priming of the immune system by up-regulating toll-like receptor (TLR) expression. Murine and cellular models of acute and chronic ozone exposure recapitulate the inflammatory effects seen in humans and enable the elucidation of key transcriptional pathways. These studies emphasize the importance of distinct transcriptional networks in driving the detrimental effects of ozone. Studies indicate the critical role of mediators including IL-1, IL-17, and IL-33 in driving ozone effects on airway inflammation, remodeling and hyperresponsiveness. Transcription analysis and proof of mechanisms studies will enable the development of drugs to ameliorate the effects of ozone exposure in susceptible individuals.

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Impact of ozone on claudins and tight junctions in the lungs

Cited by 37 publications

References 43 publications

Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk

Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk

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

Transcriptional Effects of Ozone and Impact on Airway Inflammation

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