Interferon-gamma downregulates CFTR gene expression in epithelial cells

Am J Physiol. 1994 Nov;267(5 Pt 1):C1398-404. doi: 10.1152/ajpcell.1994.267.5.C1398.


Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in defective transepithelial Cl- transport. The regulation of CF gene expression is not fully understood. We report that interferon-gamma (IFN-gamma), but not IFN-alpha or -beta, downregulates CFTR mRNA levels in two colon-derived epithelial cell lines, HT-29 and T84, in a time- and concentration (from 0.1 IU/ml)-dependent manner. IFN-gamma has no effect on the transcription rate of the CFTR gene but reduces CFTR mRNA half-life, indicating that it exerts a posttranscriptional regulation of CFTR expression, at least partly, through destabilization of the transcripts. Cells treated with IFN-gamma contain subnormal amounts of 165-kDa CFTR protein. Assays of adenosine 3',5'-cyclic monophosphate-stimulated 36Cl- efflux and whole cell currents show that CFTR function is diminished in IFN-gamma-treated cells. IFN-gamma and tumor necrosis factor-alpha synergistically reduce CFTR gene expression. Our results suggest that production of these cytokines in response to bacterial infections and inflammatory disorders may alter transmembrane Cl- transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane Permeability
  • Chlorides / metabolism
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interferon-gamma / pharmacology*
  • Interferons / pharmacology
  • Membrane Proteins / genetics*
  • Osmolar Concentration
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology


  • CFTR protein, human
  • Chlorides
  • Membrane Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Interferon-gamma
  • Interferons