Senescent fibroblasts induce moderate stress in lung epithelial cells in vitro

Exp Gerontol. 2006 May;41(5):532-9. doi: 10.1016/j.exger.2006.02.006. Epub 2006 Apr 4.

Abstract

Epithelial-mesenchymal interactions contribute to functionality and integrity of the lung epithelium, which might change during ageing and associated cellular ageing. Therefore, we studied the effect of senescent versus pre-senescent lung fibroblasts (WI-38) on mitogenic and stress-protective factors in lung epithelial cells (H358). By use of conditioned medium, we found a growth promoting impact of fibroblasts compared with control medium from epithelial cells associated with activation of ERK1/2, Akt, p70S6K, and EGF receptor. Although senescent fibroblasts mediated similar growth stimulation compared with pre-senescent cells, we observed less protection against spontaneous mitochondrial dysfunction in vitro, higher production of reactive oxygen species and activation of copper/zinc superoxide dismutase. Moreover, senescent cells induced activation of caspase-3/7 in epithelial cells, which was associated with down-regulation of the caspase-inhibitory protein XIAP. In summary, senescent lung fibroblasts induce moderate stress in lung epithelial cells in vitro without affecting growth signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication / physiology
  • Cell Death / physiology
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • Coculture Techniques
  • Culture Media, Conditioned
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology*
  • Fibroblasts / metabolism
  • Fibroblasts / physiology*
  • Humans
  • Lung / cytology*
  • Lung / metabolism
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Respiratory Mucosa / cytology
  • Signal Transduction / physiology

Substances

  • Culture Media, Conditioned
  • Reactive Oxygen Species