{"title":"8-Bromo-cAMP attenuates human airway epithelial barrier disruption caused by titanium dioxide fine and nanoparticles.","authors":"Claire E Lee, Andjela Raduka, Nannan Gao, Aabid Hussain, Fariba Rezaee","doi":"10.1080/21688370.2023.2300579","DOIUrl":null,"url":null,"abstract":"<p><p>Titanium dioxide fine particles (TiO<sub>2</sub>-FPs) and nanoparticles (TiO<sub>2</sub>-NPs) are the most widely used whitening pigments worldwide. Inhalation of TiO<sub>2</sub>-FPs and TiO<sub>2</sub>-NPs can be harmful as it triggers toxicity in the airway epithelial cells. The airway epithelium serves as the respiratory system's first line of defense in which airway epithelial cells are significant targets of inhaled pathogens and environmental particles. Our group previously found that TiO<sub>2</sub>-NPs lead to a disrupted barrier in the polarized airway epithelial cells. However, the effect of TiO<sub>2</sub>-FPs on the respiratory epithelial barrier has not been examined closely. In this study, we aimed to compare the effects of TiO<sub>2</sub>-FPs and TiO<sub>2</sub>-NPs on the structure and function of the airway epithelial barrier. Additionally, we hypothesized that 8-Bromo-cAMP, a cyclic adenosine monophosphate (cAMP) derivative, would alleviate the disruptive effects of both TiO<sub>2</sub>-FPs and TiO<sub>2</sub>-NPs. We observed increased epithelial membrane permeability in both TiO<sub>2</sub>-FPs and TiO<sub>2</sub>-NPs after exposure to 16HBE cells. Immunofluorescent labeling showed that both particle sizes disrupted the structural integrity of airway epithelial tight junctions and adherens junctions. TiO<sub>2</sub>-FPs had a slightly more, but insignificant impact on the epithelial barrier disruption than TiO<sub>2</sub>-NPs. Treatment with 8-Bromo-cAMP significantly attenuated the barrier-disrupting impact of both TiO<sub>2</sub>-FPs and TiO<sub>2</sub>-NPs on cell monolayers. Our study demonstrates that both TiO<sub>2</sub>-FPs and TiO<sub>2</sub>-NPs cause comparable barrier disruption and suggests a protective role for cAMP signaling. The observed effects of TiO<sub>2</sub>-FPs and TiO<sub>2</sub>-NPs provide a necessary understanding for characterizing the pathways involved in the defensive role of the cAMP pathway on TiO<sub>2</sub>-induced airway barrier disruption.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue Barriers","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/21688370.2023.2300579","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Titanium dioxide fine particles (TiO2-FPs) and nanoparticles (TiO2-NPs) are the most widely used whitening pigments worldwide. Inhalation of TiO2-FPs and TiO2-NPs can be harmful as it triggers toxicity in the airway epithelial cells. The airway epithelium serves as the respiratory system's first line of defense in which airway epithelial cells are significant targets of inhaled pathogens and environmental particles. Our group previously found that TiO2-NPs lead to a disrupted barrier in the polarized airway epithelial cells. However, the effect of TiO2-FPs on the respiratory epithelial barrier has not been examined closely. In this study, we aimed to compare the effects of TiO2-FPs and TiO2-NPs on the structure and function of the airway epithelial barrier. Additionally, we hypothesized that 8-Bromo-cAMP, a cyclic adenosine monophosphate (cAMP) derivative, would alleviate the disruptive effects of both TiO2-FPs and TiO2-NPs. We observed increased epithelial membrane permeability in both TiO2-FPs and TiO2-NPs after exposure to 16HBE cells. Immunofluorescent labeling showed that both particle sizes disrupted the structural integrity of airway epithelial tight junctions and adherens junctions. TiO2-FPs had a slightly more, but insignificant impact on the epithelial barrier disruption than TiO2-NPs. Treatment with 8-Bromo-cAMP significantly attenuated the barrier-disrupting impact of both TiO2-FPs and TiO2-NPs on cell monolayers. Our study demonstrates that both TiO2-FPs and TiO2-NPs cause comparable barrier disruption and suggests a protective role for cAMP signaling. The observed effects of TiO2-FPs and TiO2-NPs provide a necessary understanding for characterizing the pathways involved in the defensive role of the cAMP pathway on TiO2-induced airway barrier disruption.
期刊介绍：
Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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