Dexamethasone regulation of lung epithelial cell and fibroblast interleukin-11 production

Jingming Wang, Zhou Zhu, Robert Nolfo, Jack A. Elias

Research output: Contribution to journalArticle

Abstract

Studies were undertaken to define the effects of corticosteroids on stromal cell interleukin (IL)-11 production. Unstimulated A549 epithelial- like cells produced modest amounts of IL-11, and transforming growth factor (TGF)-β1 was a potent, dose-dependent stimulator of A549 cell IL-11 elaboration. Dexamethasone inhibited the levels of basal and TGF-β1- stimulated IL-11 elaboration in a-dose-dependent fashion. In the setting of TGF-β1 stimulation, dexamethasone caused a >90% decrease in IL-11 production at 10-6 M, a 50% decrease in IL-11 production at ~1 x 10-9 M, and significant inhibition at 10-10 M. This dexamethasone-induced inhibition was reversed by the glucocorticoid-receptor antagonist RU-486. Dexamethasone also inhibited respiratory syncytial virus, rhinovirus, and TGF-β1- stimulated IL-11 production by MRC-5 lung fibroblasts. In all cases, dexamethasone caused comparable changes in IL-11 mRNA accumulation. Nuclear run-on studies demonstrated that dexamethasone caused a modest (≤40%) decrease in TGF-β1-stimulated IL-11 gene transcription. Actinomycin D pulse- chase experiments demonstrated that dexamethasone simultaneously destabilized IL-11 mRNA. Dexamethasone also inhibited TGF-β1-stimulated IL-11 promoter- driven luciferase activity but did not diminish activator protein-1 binding to IL-11 promoter sequences. Glucocorticoids inhibit lung cell IL-11 production via a complex mechanism that involves the inhibition of IL-11 gene transcription and the destabilization of IL-11 mRNA.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume276
Issue number1 20-1
Publication statusPublished - Jan 1999
Externally publishedYes

    Fingerprint

Keywords

  • Corticosteroid
  • Fibroblast
  • Messenger ribonucleic acid degradation
  • Respiratory syncytial virus
  • Rhinovirus
  • RU- 486
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this