Effect of dexamethasone on interleukin-1beta-(IL-1beta)-induced nuclear factor-kappaB (NF-kappaB) and kappaB-dependent transcription in epithelial cells

Eur J Biochem. 1998 May 15;254(1):81-9. doi: 10.1046/j.1432-1327.1998.2540081.x.


The production of inflammatory mediators by epithelial cells in inflammatory lung diseases may represent an important target for the anti-inflammatory effects of glucocorticoids. Nuclear factor-kappaB (NF-kappaB) is a major activator of inflammatory genes and has been proposed as a target for inhibition by glucocorticoids. We have used human pulmonary type-II A549 and airway epithelial BEAS-2B cells to investigate the effect of glucocorticoids on NF-kappaB regulation and kappaB-dependent transcription. In A549 cells following interleukin-1beta (IL-1beta) treatment, there was no effect of dexamethasone on the disappearance of I kappaB alpha protein, its subsequent reappearance 90-min later or the rapid induction of I kappaB alpha mRNA and transcription rate. Expression of p65 and p50/p105 proteins were also unaffected by dexamethasone. In addition, the rapid IL-1beta-induction of NF-kappaB DNA binding and p65 nuclear localisation was unaffected by short (1-6 hours) dexamethasone pre-treatments. Similarly, BEAS-2B cells showed no effect of dexamethasone on IL-1beta-induced NF-kappaB (p50/p65). Stable transfection of a kappaB-dependent reporter in A549 cells resulted in an 8-9-fold activation by IL-1beta or phorbol ester, that was repressed 30-40% by dexamethasone. However, in these cells, IL-1beta induction of inducible nitric oxide synthase, granulocyte-macrophage colony stimulating factor and cyclooxygenase-2 mRNA showed 70-90% repression by dexamethsone. We, therefore, conclude that in these epithelial cells, the repressive effects of glucocorticoids are not mediated by up-regulation of I kappaB alpha, decreased p50/p65 gene expression or inhibition of NF-kappaB DNA binding. Furthermore, since the maximal repression of IL-1beta or phorbol-ester-induced kappaB-dependent transcription by dexamethasone was less than 40%, simple inhibition of kappaB-dependent transcription cannot by itself account for the full repressive effects of glucocorticoids observed in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cyclooxygenase 2
  • DNA-Binding Proteins / analysis
  • Dexamethasone / pharmacology*
  • Gene Expression Regulation / drug effects
  • Glucocorticoids / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Inflammation / physiopathology
  • Interleukin-1 / pharmacology*
  • Isoenzymes / metabolism
  • Lung / physiology*
  • Membrane Proteins
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Nuclear Proteins / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Messenger / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic / drug effects*
  • Transcription, Genetic / genetics
  • Transfection / genetics


  • DNA-Binding Proteins
  • Glucocorticoids
  • Interleukin-1
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • Nuclear Proteins
  • RNA, Messenger
  • Dexamethasone
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Tetradecanoylphorbol Acetate