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The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers

Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development...

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Autores principales: Che, Karlhans Fru, Tufvesson, Ellen, Tengvall, Sara, Lappi-Blanco, Elisa, Kaarteenaho, Riitta, Levänen, Bettina, Ekberg, Marie, Brauner, Annelie, Wheelock, Åsa M., Bjermer, Leif, Sköld, C. Magnus, Lindén, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365630/
https://www.ncbi.nlm.nih.gov/pubmed/29780024
http://dx.doi.org/10.1042/CS20180057
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author Che, Karlhans Fru
Tufvesson, Ellen
Tengvall, Sara
Lappi-Blanco, Elisa
Kaarteenaho, Riitta
Levänen, Bettina
Ekberg, Marie
Brauner, Annelie
Wheelock, Åsa M.
Bjermer, Leif
Sköld, C. Magnus
Lindén, Anders
author_facet Che, Karlhans Fru
Tufvesson, Ellen
Tengvall, Sara
Lappi-Blanco, Elisa
Kaarteenaho, Riitta
Levänen, Bettina
Ekberg, Marie
Brauner, Annelie
Wheelock, Åsa M.
Bjermer, Leif
Sköld, C. Magnus
Lindén, Anders
author_sort Che, Karlhans Fru
collection PubMed
description Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor κ B (NF-κB); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-κB and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples ) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.
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spelling pubmed-63656302019-02-08 The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers Che, Karlhans Fru Tufvesson, Ellen Tengvall, Sara Lappi-Blanco, Elisa Kaarteenaho, Riitta Levänen, Bettina Ekberg, Marie Brauner, Annelie Wheelock, Åsa M. Bjermer, Leif Sköld, C. Magnus Lindén, Anders Clin Sci (Lond) Research Articles Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor κ B (NF-κB); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-κB and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples ) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers. Portland Press Ltd. 2018-05-21 /pmc/articles/PMC6365630/ /pubmed/29780024 http://dx.doi.org/10.1042/CS20180057 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Che, Karlhans Fru
Tufvesson, Ellen
Tengvall, Sara
Lappi-Blanco, Elisa
Kaarteenaho, Riitta
Levänen, Bettina
Ekberg, Marie
Brauner, Annelie
Wheelock, Åsa M.
Bjermer, Leif
Sköld, C. Magnus
Lindén, Anders
The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
title The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
title_full The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
title_fullStr The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
title_full_unstemmed The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
title_short The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
title_sort neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365630/
https://www.ncbi.nlm.nih.gov/pubmed/29780024
http://dx.doi.org/10.1042/CS20180057
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