Inflammatory and Repair Pathways Induced in Human Bronchoalveolar Lavage Cells with Ozone Inhalation
| Autor: | Andrea Tham, Mehrdad Arjomandi, Chun Chen, Rachel K Stiner, Pascale Leroy, Agnès Paquet, Hofer Wong, John R. Balmes, Rachel Tenney |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Chemokine [SDV]Life Sciences [q-bio] lcsh:Medicine Inflammation Biology Proinflammatory cytokine Cell Line 03 medical and health sciences 0302 clinical medicine Endopeptidase activity Ozone Cell Movement Bronchoscopy medicine Cluster Analysis Humans Air Conditioning Osteopontin lcsh:Science ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences Multidisciplinary medicine.diagnostic_test Dose-Response Relationship Drug lcsh:R Epithelial Cells Asthma 3. Good health Oxidative Stress Bronchoalveolar lavage 030228 respiratory system Gene Expression Regulation Immunology biology.protein Cancer research lcsh:Q Cytokine secretion Female medicine.symptom Wound healing Bronchoalveolar Lavage Fluid Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2015, 10 (6), pp.e0127283. ⟨10.1371/journal.pone.0127283⟩ PLoS ONE, Vol 10, Iss 6, p e0127283 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Background Inhalation of ambient levels of ozone causes airway inflammation and epithelial injury. Methods To examine the responses of airway cells to ozone-induced oxidative injury, 19 subjects (7 with asthma) were exposed to clean air (0ppb), medium (100ppb), and high (200ppb) ambient levels of ozone for 4h on three separate occasions in a climate-controlled chamber followed by bronchoscopy with bronchoalveolar lavage (BAL) 24h later. BAL cell mRNA expression was examined using Affymetrix GeneChip Microarray. The role of a differentially expressed gene (DEG) in epithelial injury was evaluated in an in vitro model of injury [16HBE14o- cell line scratch assay]. Results Ozone exposure caused a dose-dependent up-regulation of several biologic pathways involved in inflammation and repair including chemokine and cytokine secretion, activity, and receptor binding; metalloproteinase and endopeptidase activity; adhesion, locomotion, and migration; and cell growth and tumorigenesis regulation. Asthmatic subjects had 1.7- to 3.8-fold higher expression of many DEGs suggestive of increased proinflammatory and matrix degradation and remodeling signals. The most highly up-regulated gene was osteopontin, the protein level of which in BAL fluid increased in a dose-dependent manner after ozone exposure. Asthmatic subjects had a disproportionate increase in non-polymerized osteopontin with increasing exposure to ozone. Treatment with polymeric, but not monomeric, osteopontin enhanced the migration of epithelial cells and wound closure in an α9β1 integrin-dependent manner. Conclusions Expression profiling of BAL cells after ozone exposure reveals potential regulatory genes and pathways activated by oxidative stress. One DEG, osteopontin, promotes epithelial wound healing in an in vitro model of injury. |
| Databáze: | OpenAIRE |
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