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

摘要

Sublethal oxidative stresses increase the proportions of human fibroblasts positive for senescence associated β-galactosidase activity and accelerate the transition in the fibroblast morphotypes characterising fibroblast ageing. Stimulation of fibroblasts with TNF-α or IL-1α transiently increases the production of reactive oxygen species (ROS) in human fibroblasts. Here we propose that repeated stimulation of WI-38 fibroblasts with TNF-α or IL-1α can generate enough ROS to accelerate the transition in the fibroblast morphotypes and increase the proportion of cells positive for senescence associated β-galactosidase activity. The involvement of ROS is suggested by experiments where the stimulation of fibroblasts with TNF-α or IL-1α 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-α or IL1-α is attributed to an increased ROS production occurring during the stimulation.