title: Dexamethasone inhibits repair of human airway epithelial cells mediated by glucocorticoid-induced leucine zipper (GILZ).
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jingyue
authors.initials: J
authors.lastname: Liu
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Niu
authors.forename: Zhengxiu
authors.initials: Z
authors.lastname: Luo
authors.forename: Jihong
authors.initials: J
authors.lastname: Dai
authors.forename: Lijia
authors.initials: L
authors.lastname: Wang
authors.forename: Enmei
authors.initials: E
authors.lastname: Liu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fu
mesh_terms: D001249:Asthma / Q000188:drug therapy / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014132:Trachea / Q000473:pathology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C404226:TSC22D3 protein, human; D014157:Transcription Factors; D003907:Dexamethasone