Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children.
Many asthmatic patients exhibit uncontrolled asthma despite high-dose inhaled corticosteroids (ICS). Airway epithelial cells (AEC) have distinct activation profiles that can influence ICS response.A pilot study to identify gene expression markers of AEC dysfunction and markers of corticosteroid sens...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5426685?pdf=render |
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| author | Michael Fayon Aurelie Lacoste-Rodrigues Pascal Barat Jean-Christophe Helbling Fabienne Nacka Patrick Berger Marie-Pierre Moisan Jean-Benoit Corcuff |
| author_facet | Michael Fayon Aurelie Lacoste-Rodrigues Pascal Barat Jean-Christophe Helbling Fabienne Nacka Patrick Berger Marie-Pierre Moisan Jean-Benoit Corcuff |
| author_sort | Michael Fayon |
| collection | DOAJ |
| description | Many asthmatic patients exhibit uncontrolled asthma despite high-dose inhaled corticosteroids (ICS). Airway epithelial cells (AEC) have distinct activation profiles that can influence ICS response.A pilot study to identify gene expression markers of AEC dysfunction and markers of corticosteroid sensitivity in asthmatic and non-asthmatic control children, for comparison with published reports in adults.AEC were obtained by nasal brushings and primary submerged cultures, and incubated in control conditions or in the presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both. RT-PCR-based expression of FKBP51 (a steroid hormone receptor signalling regulator), NF-kB, IL-6, LIF (an IL-6 family neurotrophic cytokine), serpinB2 (which inhibits plasminogen activation and promotes fibrin deposition) and porin (a marker of mitochondrial mass) were determined.6 patients without asthma (median age 11yr; min-max: 7-13), 8 with controlled asthma (11yr, 7-13; median daily fluticasone dose = 100 μg), and 4 with uncontrolled asthma (12yr, 7-14; 1000 μg fluticasone daily) were included. Baseline expression of LIF mRNA was significantly increased in uncontrolled vs controlled asthmatic children. TNFalpha significantly increased LIF expression in uncontrolled asthma. A similar trend was observed regarding IL-6. Dexamethasone significantly upregulated FKBP51 expression in all groups but the response was blunted in asthmatic children. No significant upregulation was identified regarding NF-kB, serpinB2 and porin.LIF and FKBP51 expression in epithelial cells were the most interesting markers of AEC dysfunction/response to corticosteroid treatment. |
| first_indexed | 2024-12-21T13:07:24Z |
| format | Article |
| id | doaj.art-0397714d019141a8972b875cc396985d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T13:07:24Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0397714d019141a8972b875cc396985d2022-12-21T19:02:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017705110.1371/journal.pone.0177051Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children.Michael FayonAurelie Lacoste-RodriguesPascal BaratJean-Christophe HelblingFabienne NackaPatrick BergerMarie-Pierre MoisanJean-Benoit CorcuffMany asthmatic patients exhibit uncontrolled asthma despite high-dose inhaled corticosteroids (ICS). Airway epithelial cells (AEC) have distinct activation profiles that can influence ICS response.A pilot study to identify gene expression markers of AEC dysfunction and markers of corticosteroid sensitivity in asthmatic and non-asthmatic control children, for comparison with published reports in adults.AEC were obtained by nasal brushings and primary submerged cultures, and incubated in control conditions or in the presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both. RT-PCR-based expression of FKBP51 (a steroid hormone receptor signalling regulator), NF-kB, IL-6, LIF (an IL-6 family neurotrophic cytokine), serpinB2 (which inhibits plasminogen activation and promotes fibrin deposition) and porin (a marker of mitochondrial mass) were determined.6 patients without asthma (median age 11yr; min-max: 7-13), 8 with controlled asthma (11yr, 7-13; median daily fluticasone dose = 100 μg), and 4 with uncontrolled asthma (12yr, 7-14; 1000 μg fluticasone daily) were included. Baseline expression of LIF mRNA was significantly increased in uncontrolled vs controlled asthmatic children. TNFalpha significantly increased LIF expression in uncontrolled asthma. A similar trend was observed regarding IL-6. Dexamethasone significantly upregulated FKBP51 expression in all groups but the response was blunted in asthmatic children. No significant upregulation was identified regarding NF-kB, serpinB2 and porin.LIF and FKBP51 expression in epithelial cells were the most interesting markers of AEC dysfunction/response to corticosteroid treatment.http://europepmc.org/articles/PMC5426685?pdf=render |
| spellingShingle | Michael Fayon Aurelie Lacoste-Rodrigues Pascal Barat Jean-Christophe Helbling Fabienne Nacka Patrick Berger Marie-Pierre Moisan Jean-Benoit Corcuff Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children. PLoS ONE |
| title | Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children. |
| title_full | Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children. |
| title_fullStr | Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children. |
| title_full_unstemmed | Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children. |
| title_short | Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children. |
| title_sort | nasal airway epithelial cell il 6 and fkbp51 gene expression and steroid sensitivity in asthmatic children |
| url | http://europepmc.org/articles/PMC5426685?pdf=render |
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