Show simple item record

dc.contributor.authorO'NEILL, LUKEen
dc.contributor.authorBOWIE, ANDREWen
dc.date.accessioned2009-09-30T22:05:19Z
dc.date.available2009-09-30T22:05:19Z
dc.date.issued2000en
dc.date.submitted2000en
dc.identifier.citationA. G. Bowie and L. A. O'Neill, Vitamin C inhibits NF-kappa B activation by TNF via the activation of p38 mitogen-activated protein kinase, Journal of Immunology, 165, 12, 2000, 7180-7188en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/33699
dc.descriptionPUBLISHEDen
dc.descriptionPMID: 11120850en
dc.description.abstractThe transcription factor NF-kappaB is a central mediator of altered gene expression during inflammation, and is implicated in a number of pathologies, including cancer, atherosclerosis, and viral infection. We report in this study that vitamin C inhibits the activation of NF-kappaB by multiple stimuli, including IL-1 and TNF in the endothelial cell line ECV304 and in primary HUVECs. The induction of a NF-kappaB-dependent gene, IL-8, by TNF was also inhibited. The effect requires millimolar concentrations of vitamin C, which occur intracellularly in vivo, particularly during inflammation. Vitamin C was not toxic to cells, did not inhibit another inducible transcription factor, STAT1, and had no effect on the DNA binding of NF-kappaB. Inhibition by vitamin C was not simply an antioxidant effect, because redox-insensitive pathways to NF-kappaB were also blocked. Vitamin C was shown to block IL-1- and TNF-mediated degradation and phosphorylation of I-kappaBalpha (inhibitory protein that dissociates from NF-kappaB), due to inhibition of I-kappaB kinase (IKK) activation. Inhibition of TNF-driven IKK activation was mediated by p38 mitogen-activated protein kinase, because treatment of cells with vitamin C led to a rapid and sustained activation of p38, and the specific p38 inhibitor SB203580 reversed the inhibitory effect of vitamin C on IKK activity, I-kappaBalpha phosphorylation, and NF-kappaB activation. The results identify p38 as an intracellular target for high dose vitamin C.en
dc.description.sponsorshipThis work was supported by the European Union (EU) Biotech Program, Contract Number BMH4-CT97-2453.en
dc.format.extent7180-7188en
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.relation.ispartofseriesJournal of Immunologyen
dc.relation.ispartofseries165en
dc.relation.ispartofseries12en
dc.rightsYen
dc.subjectBiochemistryen
dc.titleVitamin C inhibits NF-kappa B activation by TNF via the activation of p38 mitogen-activated protein kinaseen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/laoneillen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/agbowieen
dc.identifier.rssinternalid20845en
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.subject.TCDThemeNeuroscienceen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record