title: The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells.
abstract: BACKGROUND
  Nuclear factor kappaB (NF-kappaB) plays a key role in the pathogenesis of asthma, being linked to the production of inflammatory cytokines that drive inflammation. A recently described anti-inflammatory protein, glucocorticoid-induced leucine zipper (GILZ), interferes with NF-kappaB-mediated gene transcription in T cells and macrophages.
  
  
  OBJECTIVE
  We sought to analyze the regulation of GILZ expression in airway epithelial cells and determine whether GILZ mediates part of the anti-inflammatory effect of corticosteroids.
  
  
  METHODS
  GILZ expression was assessed by means of PCR and immunoblotting in human epithelial cells at baseline and after stimulation with dexamethasone or cytokines (IL-1beta, TNF-alpha, and IFN-gamma). The effect of GILZ on LPS-, IL-1beta-, and polyinosinic:polycytidylic acid-induced NF-kappaB activation was assessed in BEAS-2B cells overexpressing GILZ. The requirement for GILZ in the inhibitory action of dexamethasone was assessed by knocking down GILZ expression by means of small interfering RNA (siRNA) technology.
  
  
  RESULTS
  GILZ is constitutively expressed by human airway epithelial cells, and its levels are increased by dexamethasone and decreased by inflammatory cytokines. Overexpression of GILZ in BEAS-2B cells significantly inhibited the ability of IL-1beta, LPS, and polyinosinic:polycytidylic acid to activate NF-kappaB, whereas knockdown of GILZ inhibited the ability of dexamethasone to suppress IL-1beta-induced chemokine expression.
  
  
  CONCLUSIONS
  This study demonstrates the expression of GILZ in human airway epithelial cells, its induction by dexamethasone, its suppression by inflammatory cytokines, and its role in mediating the anti-inflammatory effects of dexamethasone.
  
  
  CONCLUSIONS
  Therapeutic upregulation of GILZ may be a novel strategy for the treatment of asthma.
authors.affiliation: Veterans Medical Research Foundation, La Jolla, CA, USA. jeddleston@vapop.ucsd.edu
authors.forename: Jane
authors.initials: J
authors.lastname: Eddleston
authors.forename: Jack
authors.initials: J
authors.lastname: Herschbach
authors.forename: Amy L
authors.initials: AL
authors.lastname: Wagelie-Steffen
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Christiansen
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Zuraw
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; C404226:TSC22D3 protein, human; D014157:Transcription Factors; D003907:Dexamethasone