Pro-inflammatory cytokines induce c-fos expression followed by IL-6 release in human airway smooth muscle cells

Mediators Inflamm. 2001 Jun;10(3):135-42. doi: 10.1080/09629350124155.

Abstract

Background: Airway smooth muscle (ASM) is considered to be a target for mediators released during airway inflammation.

Aims: To investigate the expression of c-fos, a constituent of the transcription factor activator protein-1, in human ASM cells. In addition, to measure the release of interleukin (IL)-6 into the conditioned medium of stimulated ASM cells, as well as DNA biosynthesis and changes in cell number.

Methods: Serum-deprived human ASM cells in the G0/G1 phase were stimulated with the pro-inflammatory cytokines; tumour necrosis factor-alpha, IL-1beta, IL-5 and IL-6. The expression of mRNA encoding the proto-oncogene c-fos was measured by Northern blot analysis. Cell proliferation was assessed by [3H]-thymidine incorporation assays and cell counting, and IL-6 levels in cell-conditioned medium were measured by enzyme-linked immunosorbent assay.

Results: All of the cytokines investigated induced a rapid (within 1 h) and transient increase in the expression of mRNA encoding c-fos, followed by the expression and enhanced release of IL-6. Cell proliferation remained unchanged in cytokine-stimulated cells.

Conclusions: Cytokine-induced c-fos expression in human ASM cells could be described as a marker of cell 'activation'. The possible association of these results with airway inflammation, through secondary intracellular mechanisms such as cytokine production, is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchi / cytology
  • Cell Count
  • Cells, Cultured
  • Culture Media, Conditioned
  • Gene Expression / drug effects
  • Gene Expression / immunology*
  • Humans
  • Interleukin-1 / immunology*
  • Interleukin-1 / pharmacology
  • Interleukin-5 / immunology*
  • Interleukin-5 / pharmacology
  • Interleukin-6 / immunology*
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / immunology*
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogenes
  • Thymidine / metabolism
  • Tritium
  • Tumor Necrosis Factor-alpha / immunology*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Culture Media, Conditioned
  • Interleukin-1
  • Interleukin-5
  • Interleukin-6
  • Proto-Oncogene Proteins c-fos
  • Tumor Necrosis Factor-alpha
  • Tritium
  • Thymidine