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.
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.
Dumont
P
P
Unit of Cellular Biochemistry and Biology, University of Namur (FUNDP), Belgium.
Balbeur
L
L
Remacle
J
J
Toussaint
O
O
D000111:Acetylcysteine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000648:ultrastructure; D048429:Cell Size; D003593:Cytoplasm / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007375:Interleukin-1 / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000032:analysis
D015415:Biomarkers; D007375:Interleukin-1; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D001616:beta-Galactosidase; D000111:Acetylcysteine