Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children.
PLoS ONE. 2017-05-11; 12(5): e0177051
DOI: 10.1371/journal.pone.0177051
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Fayon M(1)(2), Lacoste-Rodrigues A(1)(2), Barat P(2)(3), Helbling JC(3)(4), Nacka F(2), Berger P(1)(2), Moisan MP(3)(4), Corcuff JB(3)(4).
Author information:
(1)Université de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Bordeaux, France.
(2)CHU de Bordeaux, Centre d’Investigation Clinique (CIC 1401), Bordeaux, France.
(3)Université de Bordeaux, Nutrition and Integrative Neurobiology, Bordeaux, France.
(4)INRA, UMR1286, Nutrition and Integrative Neurobiology, Bordeaux, France.
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.
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.
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.
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.
CONCLUSION: LIF and FKBP51 expression in epithelial cells were the most
interesting markers of AEC dysfunction/response to corticosteroid treatment.