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Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells
Background: Exposure to ambient air particulate matter (PM) has been shown to increase rates of cardiopulmonary morbidity and mortality, but the underlying mechanisms are still not well understood. Objective: We examined signaling events involved in the expression of the inflammatory gene interleuki...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Institute of Environmental Health Sciences
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230452/ https://www.ncbi.nlm.nih.gov/pubmed/21665565 http://dx.doi.org/10.1289/ehp.1103594 |
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author | Silbajoris, Robert Osornio-Vargas, Alvaro R. Simmons, Steven O. Reed, William Bromberg, Philip A. Dailey, Lisa A. Samet, James M. |
author_facet | Silbajoris, Robert Osornio-Vargas, Alvaro R. Simmons, Steven O. Reed, William Bromberg, Philip A. Dailey, Lisa A. Samet, James M. |
author_sort | Silbajoris, Robert |
collection | PubMed |
description | Background: Exposure to ambient air particulate matter (PM) has been shown to increase rates of cardiopulmonary morbidity and mortality, but the underlying mechanisms are still not well understood. Objective: We examined signaling events involved in the expression of the inflammatory gene interleukin-8 (IL-8) in human airway epithelial cells (HAECs) exposed to ambient PM collected in an urban area of Mexicali, Mexico. Methods: We studied IL-8 expression and regulatory signaling pathways in cultured HAECs exposed to Mexicali PM suspended in media for 0–4 hr. Results: Exposure resulted in a dose-dependent, 2- to 8-fold increase in IL-8 mRNA expression relative to controls. PM exposure induced IL-8 transcriptional activity in BEAS-2B cells that was dependent on the nuclear factor-kappa B (NF-κB) response element in the IL-8 promoter. Chromatin immunoprecipitation (ChIP) assays showed a 3-fold increase in binding of the p65 (RelA) NF-κB isoform to the IL-8 promoter sequence in HAECs exposed to PM. Western blot analyses showed elevated levels of phosphorylation of p65 but no changes in IκBα phosphorylation or degradation. IL-8 expression was blunted in a dose-dependent manner in BEAS-2B cells transduced with a lentivirus encoding a dominant negative p65 mutant in which phosphorylation sites were inactivated. Conclusion: Taken together, these findings show that the increase in IL-8 mRNA expression in HAECs exposed to PM(10) (PM ≤ 10 μm in aerodynamic diameter) is mediated through an NF-κB–dependent signaling mechanism that occurs through a pathway involving direct phosphorylation of the transcription factor p65 in the absence of IκBα degradation. These data show that exposure to PM(10) in ambient air can induce inflammatory responses by activating specific signaling mechanisms in HAECs. |
format | Online Article Text |
id | pubmed-3230452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | National Institute of Environmental Health Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-32304522011-12-15 Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells Silbajoris, Robert Osornio-Vargas, Alvaro R. Simmons, Steven O. Reed, William Bromberg, Philip A. Dailey, Lisa A. Samet, James M. Environ Health Perspect Research Background: Exposure to ambient air particulate matter (PM) has been shown to increase rates of cardiopulmonary morbidity and mortality, but the underlying mechanisms are still not well understood. Objective: We examined signaling events involved in the expression of the inflammatory gene interleukin-8 (IL-8) in human airway epithelial cells (HAECs) exposed to ambient PM collected in an urban area of Mexicali, Mexico. Methods: We studied IL-8 expression and regulatory signaling pathways in cultured HAECs exposed to Mexicali PM suspended in media for 0–4 hr. Results: Exposure resulted in a dose-dependent, 2- to 8-fold increase in IL-8 mRNA expression relative to controls. PM exposure induced IL-8 transcriptional activity in BEAS-2B cells that was dependent on the nuclear factor-kappa B (NF-κB) response element in the IL-8 promoter. Chromatin immunoprecipitation (ChIP) assays showed a 3-fold increase in binding of the p65 (RelA) NF-κB isoform to the IL-8 promoter sequence in HAECs exposed to PM. Western blot analyses showed elevated levels of phosphorylation of p65 but no changes in IκBα phosphorylation or degradation. IL-8 expression was blunted in a dose-dependent manner in BEAS-2B cells transduced with a lentivirus encoding a dominant negative p65 mutant in which phosphorylation sites were inactivated. Conclusion: Taken together, these findings show that the increase in IL-8 mRNA expression in HAECs exposed to PM(10) (PM ≤ 10 μm in aerodynamic diameter) is mediated through an NF-κB–dependent signaling mechanism that occurs through a pathway involving direct phosphorylation of the transcription factor p65 in the absence of IκBα degradation. These data show that exposure to PM(10) in ambient air can induce inflammatory responses by activating specific signaling mechanisms in HAECs. National Institute of Environmental Health Sciences 2011-06-10 2011-10 /pmc/articles/PMC3230452/ /pubmed/21665565 http://dx.doi.org/10.1289/ehp.1103594 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright. |
spellingShingle | Research Silbajoris, Robert Osornio-Vargas, Alvaro R. Simmons, Steven O. Reed, William Bromberg, Philip A. Dailey, Lisa A. Samet, James M. Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells |
title | Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells |
title_full | Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells |
title_fullStr | Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells |
title_full_unstemmed | Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells |
title_short | Ambient Particulate Matter Induces Interleukin-8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells |
title_sort | ambient particulate matter induces interleukin-8 expression through an alternative nf-κb (nuclear factor-kappa b) mechanism in human airway epithelial cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230452/ https://www.ncbi.nlm.nih.gov/pubmed/21665565 http://dx.doi.org/10.1289/ehp.1103594 |
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