Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children

PLoS One. 2017 May 11;12(5):e0177051. doi: 10.1371/journal.pone.0177051. eCollection 2017.


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.

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use*
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / genetics*
  • Asthma / pathology
  • Child
  • Female
  • Humans
  • Interleukin-6 / genetics*
  • Leukemia Inhibitory Factor / genetics
  • Male
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / pathology*
  • Pilot Projects
  • RNA, Messenger / genetics
  • Tacrolimus Binding Proteins / genetics*


  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • RNA, Messenger
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5

Grants and funding

The authors received no specific funding for this work.