Interferon-gamma stimulates fractalkine expression in human bronchial epithelial cells and regulates mononuclear cell adherence

Am J Respir Cell Mol Biol. 2001 Aug;25(2):233-8. doi: 10.1165/ajrcmb.25.2.4275.

Abstract

Bronchial epithelial cells may contribute to airway inflammation by releasing chemokines and expressing surface membrane molecules involved in the adhesion of leukocytes. We found that interferon (IFN)-gamma stimulates expression of fractalkine, a potent chemoattractant for monocytes and T lymphocytes, in a time- and concentration-dependent manner by normal human bronchial epithelial cells in culture. Enhanced expression of fractalkine messenger RNA was confirmed by both reverse transcription/polymerase chain reaction and Northern blotting. IFN-gamma also stimulated fractalkine protein production and most of the protein was found in cell lysates. The adherence of blood mononuclear cells to the monolayers of bronchial epithelial cells stimulated with IFN-gamma was partly inhibited by an antifractalkine antibody. An antibody against intercellular adhesion molecule-1 was similarly effective in inhibiting the adhesion. Fractalkine protein levels in bronchoalveolar lavage fluids from patients with inflammatory diseases correlated positively with mononuclear cell counts in the fluids. The bronchial epithelium in a biopsy specimen of lung cancer was stained positively by immunofluorescent staining for fractalkine. We conclude that IFN-gamma stimulates fractalkine expression by bronchial epithelial cells, which may play an important role in inflammatory responses by recruiting mononuclear leukocytes to the bronchial epithelium.

MeSH terms

  • Base Sequence
  • Bronchi / drug effects*
  • Bronchi / metabolism*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cell Adhesion / drug effects
  • Cells, Cultured
  • Chemokine CX3CL1
  • Chemokines, CX3C / genetics*
  • Chemokines, CX3C / metabolism
  • DNA Primers / genetics
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Humans
  • Interferon-gamma / pharmacology*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • DNA Primers
  • Membrane Proteins
  • RNA, Messenger
  • Interferon-gamma