Appearance of biomarkers of in vitro ageing after successive stimulation of WI-38 fibroblasts with IL-1alpha and TNF-alpha: senescence associated beta-galactosidase activity and morphotype transition

J Anat. 2000 Nov;197 Pt 4(Pt 4):529-37. doi: 10.1046/j.1469-7580.2000.19740529.x.

Abstract

Sublethal oxidative stresses increase the proportions of human fibroblasts positive for senescence associated beta-galactosidase activity and accelerate the transition in the fibroblast morphotypes characterising fibroblast ageing. Stimulation of fibroblasts with TNF-alpha or IL-1alpha transiently increases the production of reactive oxygen species (ROS) in human fibroblasts. Here we propose that repeated stimulation of WI-38 fibroblasts with TNF-alpha or IL-1alpha can generate enough ROS to accelerate the transition in the fibroblast morphotypes and increase the proportion of cells positive for senescence associated beta-galactosidase activity. The involvement of ROS is suggested by experiments where the stimulation of fibroblasts with TNF-alpha or IL-1alpha are performed in the presence of N-acetylcysteine which increases the intracellular antioxidant potential. It is proposed that the decrease in the proportions of morphotypes I and II, and the increase in the proportions of morphotypes III to VI observed after successive stimulation with TNF-alpha or IL1-alpha is attributed to an increased ROS production occurring during the stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Aging / physiology*
  • Biomarkers / analysis
  • Cell Division / drug effects
  • Cell Line
  • Cell Nucleus / ultrastructure
  • Cell Size
  • Cytoplasm / ultrastructure
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Humans
  • Image Processing, Computer-Assisted
  • Interleukin-1 / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Stimulation, Chemical
  • Tumor Necrosis Factor-alpha / pharmacology*
  • beta-Galactosidase / analysis

Substances

  • Biomarkers
  • Interleukin-1
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • beta-Galactosidase
  • Acetylcysteine