title: Oncogene- and oxidative stress-induced cellular senescence shows distinct expression patterns of proinflammatory cytokines in vascular endothelial cells.
abstract: Senescent cells are metabolically active and produce a variety of proinflammatory cytokines. It was previously reported that atherosclerotic plaques contain senescent cells, suggesting that senescence may contribute to the progression of atherosclerosis. In this study, we induced cellular senescence in vascular endothelial cells (VECs) using hydrogen peroxide (H₂O₂) or an adenovirus that expresses a constitutively active mutant of Ras (AdRas12V) and studied the expression of cytokines. Both H₂O₂ treatment and AdRas12V infection induced senescence in VECs, as assessed by senescence-associated β-Gal activity and the expression of proteins such as p53 and p21(CIP1). In addition, both treatments induced the expression of a variety of cytokines, including interleukin-1β (IL-1β) and nerve growth factor (NGF). AdRas12V infection induced IL-1β expression more significantly than H₂O₂ treatment, whereas both treatments induced comparable mRNA and protein expression levels of NGF. These results suggest that senescent cells express different patterns of proinflammatory cytokines, depending on the trigger that induced senescence. It is therefore possible that senescent cells can differentially induce inflammation in the surrounding tissues, depending on the cause of senescence.
authors.affiliation: Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512, Japan.
authors.forename: Etsu
authors.initials: E
authors.lastname: Suzuki
authors.forename: Masao
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Oba
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
mesh_terms: D016922:Cellular Senescence / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007249:Inflammation; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D011993:Recombinant Fusion Proteins; D020932:Nerve Growth Factor; D006861:Hydrogen Peroxide; D016283:Proto-Oncogene Proteins p21(ras)