Activation of RelA homodimers by tumour necrosis factor α: a possible transcriptional activator in human vascular endothelial cells

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Activation of RelA homodimers by tumour necrosis factor α: a possible transcriptional activator in human vascular endothelial cells

Publisher
Portland Press Ltd.
Publication Date
Aug 09, 2005
Source
PMC
Keywords
Disciplines
  • Biology
License
Unknown

Abstract

bic979.dvi Biochem. J. (2005) 390, 317–324 (Printed in Great Britain) doi:10.1042/BJ20041659 317 Activation of RelA homodimers by tumour necrosis factor α: a possible transcriptional activator in human vascular endothelial cells Nobuyuki MARUI1, Russell M. MEDFORD2 and Mushtaq AHMAD3 Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, U.S.A. In vascular endothelial cells, cytokines induce genes that are ex- pressed in inflammatory lesions partly through the activation of transcription factor NF-κB (nuclear factor-κB). Among the mem- bers of the NF-κB/rel protein family, homodimers of the RelA subunit of NF-κB can also function as strong transactivators when expressed in cells. However, the functional role of endogenous RelA homodimers has not been clearly elucidated. We investi- gated whether RelA homodimers are induced in cytokine-treated vascular endothelial cells. Gel mobility-shift and supershift assays revealed that a cytokine TNFα (tumour necrosis factor α) ac- tivated both NF-κB1/RelA heterodimers and RelA homodimers that bound to a canonical κB sequence, IgκB (immunoglobulin κB), in SV40 (simian virus 40) immortalized HMEC-1 (human dermal microvascular endothelial cell line 1). In HMEC-1 and HUVEC (human umbilical-vein endothelial cells), TNFα also induced RelA homodimers that bound to the sequence 65-2κB, which specifically binds to RelA homodimers but not to NF-κB1/ RelA heterodimers in vitro. Deoxycholic acid, a detergent that can dissociate the NF-κB–IκB complex (where IκB stands for inhibitory κB), induced the binding of the RelA homodimers to 65-2κB from the cytosolic fraction of resting HMEC-1. Furthermore, TNFα induced the transcriptional activity of a reporter gene that was driven by 65-2κB in HMEC-1. These results suggest that in addition to NF-κB1/RelA heterodimers, TNFα also induces RelA homodimers that are functionally active. Thus RelA homodimers may actively participate in cytokine regulation of gene expression in human vascular endothe

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