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Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children.
- Source :
-
PloS one [PLoS One] 2017 May 11; Vol. 12 (5), pp. e0177051. Date of Electronic Publication: 2017 May 11 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- Background: 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.<br />Objectives: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusion: LIF and FKBP51 expression in epithelial cells were the most interesting markers of AEC dysfunction/response to corticosteroid treatment.
- Subjects :
- Adolescent
Asthma pathology
Child
Female
Humans
Leukemia Inhibitory Factor genetics
Male
Nasal Mucosa drug effects
Nasal Mucosa metabolism
Pilot Projects
RNA, Messenger genetics
Adrenal Cortex Hormones therapeutic use
Anti-Asthmatic Agents therapeutic use
Asthma drug therapy
Asthma genetics
Interleukin-6 genetics
Nasal Mucosa pathology
Tacrolimus Binding Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28493984
- Full Text :
- https://doi.org/10.1371/journal.pone.0177051