Influence of IFN-gamma on gene expression in normal human bronchial epithelial cells: modulation of IFN-gamma effects by dexamethasone

Physiol Genomics. 2005 Sep 21;23(1):28-45. doi: 10.1152/physiolgenomics.00011.2005. Epub 2005 Jun 28.


Interferon gamma (IFN-gamma) plays a role in a variety of lung inflammatory responses, and corticosteroids are frequently employed as a treatment in these conditions. Therefore, the effect of IFN-gamma, of the corticosteroid dexamethasone (Dex), or of both on gene expression was studied in normal human bronchial epithelial (NHBE) cells. NHBE cells were exposed to medium alone, IFN-gamma (300 U/ml), Dex (10(-7) M), or both IFN-gamma and Dex for 8 or 24 h. Gene expression was examined using oligonucleotide microarrays. A principal components analysis demonstrated that the IFN-gamma treatment effect was the primary source of differences in the data. With a 5% false discovery rate, of the 66 genes upregulated by IFN-gamma by twofold or greater at 8 h and 287 genes upregulated at 24 h, coincubation with Dex inhibited the expression of 2 genes at 8 h and 45 genes at 24 h. Prominent among these were cytokines and secreted proteins. Dex cotreatment increased expression of 65 of the 376 genes that were inhibited by IFN-gamma by 50% at 24 h. The majority of these genes encode cell cycle or nuclear proteins. Dex alone increased the expression of only 22 genes and inhibited the expression of 7 genes compared with controls at 24 h. The effect of Dex on IFN-gamma-induced changes suggests a specific, targeted effect on IFN-gamma responses that is substantially greater than the effect of Dex alone. Dex had little effect on the immediate early response to IFN-gamma but a significant effect on the late responses.

MeSH terms

  • Adrenal Cortex Hormones / metabolism
  • Bronchi / cytology*
  • Bronchi / metabolism
  • Cell Cycle
  • Cell Differentiation
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Chemokine CCL5 / metabolism
  • Cluster Analysis
  • Culture Media / metabolism
  • Cytokines / metabolism
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Epithelial Cells / metabolism*
  • Gene Expression
  • Gene Expression Regulation*
  • Glucocorticoids / metabolism
  • Humans
  • Inflammation
  • Interferon-gamma / chemistry
  • Interferon-gamma / metabolism*
  • Interferons / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Oligonucleotides / chemistry
  • Quality Control
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • T-Lymphocytes / metabolism
  • Time Factors
  • Transcription, Genetic
  • Up-Regulation


  • Adrenal Cortex Hormones
  • Chemokine CCL2
  • Chemokine CCL5
  • Culture Media
  • Cytokines
  • Glucocorticoids
  • Oligonucleotides
  • Recombinant Proteins
  • Dexamethasone
  • Interferon-gamma
  • Interferons