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In endothelial cells, this phenomenon might contribute to vascular disease. Plasma levels of the inflammatory cytokine tumor necrosis factor alpha (TNF\u03b1) are increased in age-related and chronic conditions such as atherosclerosis, rheumatoid arthritis, psoriasis, and Crohn\u2019s disease. Although TNF\u03b1 is a known activator of the central inflammatory mediator NF-\u03baB, and can induce the intracellular generation of reactive oxygen species (ROS), the question whether TNF\u03b1 can induce senescence has not been answered conclusively. Here, we investigated the effect of prolonged TNF\u03b1 exposure on the fate of endothelial cells and found that such treatment induced premature senescence. Induction of endothelial senescence was prevented by the anti-oxidant N-acetyl cysteine, as well as by plumericin and PHA-408, inhibitors of the NF-\u03baB pathway. Our results indicated that prolonged TNF\u03b1 exposure could have detrimental consequences to endothelial cells by causing senescence and, therefore, chronically increased TNF\u03b1 levels might possibly contribute to the pathology of chronic inflammatory diseases by driving premature endothelial senescence.<\/jats:p>","DOI":"10.1038\/srep39501","type":"journal-article","created":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T11:35:05Z","timestamp":1483443305000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":142,"title":["Premature senescence of endothelial cells upon chronic exposure to TNF\u03b1 can be prevented by N-acetyl cysteine and plumericin"],"prefix":"10.1038","volume":"7","author":[{"given":"Shafaat Y.","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezzat M.","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Oszwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mayr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoke","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Waltenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Stuppner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Lipovac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Uhrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M.","family":"Breuss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,3]]},"reference":[{"key":"BFsrep39501_CR1","unstructured":"National Center for Health, S. 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