Dexamethasone inhibits repair of human airway epithelial cells mediated by glucocorticoid-induced leucine zipper (GILZ)

PLoS One. 2013;8(4):e60705. doi: 10.1371/journal.pone.0060705. Epub 2013 Apr 3.


Background: Glucocorticoids (GCs) are a first-line treatment for asthma for their anti-inflammatory effects, but they also hinder the repair of airway epithelial injury. The anti-inflammatory protein GC-induced leucine zipper (GILZ) is reported to inhibit the activation of the mitogen-activated protein kinase (MAPK)-extracellular-signal-regulated kinase (ERK) signaling pathway, which promotes the repair of airway epithelial cells around the damaged areas. We investigated whether the inhibition of airway epithelial repair imposed by the GC dexamethasone (DEX) is mediated by GILZ.

Methods: We tested the effect of DEX on the expressions of GILZ mRNA and GILZ protein and the MAPK-ERK signaling pathway in human airway epithelial cells, via RT-PCR and Western blot. We further evaluated the role of GILZ in mediating the effect of DEX on the MAPK-ERK signaling pathway and in airway epithelium repair by utilizing small-interfering RNAs, MTT, CFSE labeling, wound-healing and cell migration assays.

Results: DEX increased GILZ mRNA and GILZ protein levels in a human airway epithelial cell line. Furthermore, DEX inhibited the phosphorylation of Raf-1, Mek1/2, Erk1/2 (components of the MAPK-ERK signaling pathway), proliferation and migration. However, the inhibitory effect of DEX was mitigated in cells when the GILZ gene was silenced.

Conclusions: The inhibition of epithelial injury repair by DEX is mediated in part by activation of GILZ, which suppressed activation of the MAPK-ERK signaling pathway, proliferation and migration. Our study implicates the involvement of DEX in this process, and furthers our understanding of the dual role of GCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / drug therapy
  • Asthma / pathology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dexamethasone / pharmacology*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / physiology
  • Gene Expression / drug effects
  • Gene Knockdown Techniques
  • Glucocorticoids / pharmacology*
  • Humans
  • MAP Kinase Signaling System
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Trachea / pathology
  • Transcription Factors / physiology*


  • Glucocorticoids
  • RNA, Messenger
  • RNA, Small Interfering
  • TSC22D3 protein, human
  • Transcription Factors
  • Dexamethasone

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (number 81070014) and Chongqing Municipal Health Bureau (number 2010-1-46). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.