TWEAK/Fn14 interaction stimulates human bronchial epithelial cells to produce IL-8 and GM-CSF

Biochem Biophys Res Commun. 2004 May 28;318(2):422-7. doi: 10.1016/j.bbrc.2004.04.036.

Abstract

TNF-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family, is a multifunctional cytokine that regulates cellular proliferation, angiogenesis, inflammation, and apoptosis. In this study, we investigated the effect of TWEAK on human bronchial epithelial cells. A human bronchial epithelial cell line, BEAS2B, expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced IL-8 and GM-CSF upon TWEAK stimulation in a dose-dependent manner, which was abrogated by anti-Fn14 blocking antibody. TWEAK induced phosphorylation of IkappaBalpha and BAY11-7082, a selective inhibitor of IkappaBalpha phosphorylation, inhibited the TWEAK-induced IL-8 and GM-CSF production by BEAS2B cells. Moreover, primary cultured human bronchial epithelial cells also expressed Fn14 and produced IL-8 and GM-CSF upon TWEAK stimulation. Collectively, TWEAK stimulated human bronchial epithelial cells to produce IL-8 and GM-CSF through Fn14. Because IL-8 and GM-CSF are associated with inflammatory conditions, these results suggest that TWEAK/Fn14 interaction may play some roles in airway inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / metabolism*
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology*
  • Cell Line
  • Cell Membrane / metabolism
  • Cytokine TWEAK
  • Dose-Response Relationship, Drug
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Flow Cytometry
  • Gene Expression / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Humans
  • I-kappa B Proteins / metabolism
  • Interleukin-8 / biosynthesis*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / metabolism*
  • Phosphorylation
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • TWEAK Receptor
  • Tumor Necrosis Factors

Substances

  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cytokine TWEAK
  • I-kappa B Proteins
  • Interleukin-8
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • TNFRSF12A protein, human
  • TNFSF12 protein, human
  • TWEAK Receptor
  • Tumor Necrosis Factors
  • Granulocyte-Macrophage Colony-Stimulating Factor