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Author Notes:

To whom correspondence should be addressed (email mahmad@emory.edu).

N.M. Present address: Division of Cardiology, Chubu Rosai Hospital, 1-10-6, Komei, Minato-ku, Nagoya, 455-0018, Japan.

R.M. Present address: AtheroGenics, Inc., 8995 Westside Parkway, Alpharetta, GA 30004, U.S.A.


Research Funding:

This work was supported by research grants NIH RO1 HL-66508-01 (to M.A.) and NIH PO1-HL48667 (to R.M.M. and R. Wayne Alexander).


  • cytokine
  • endothelial cell
  • microvascular
  • nuclear factor-κB1 (NF-κB1)
  • RelA homodimer
  • tumour necrosis factor α (TNFα)
  • CAT, chloramphenicol acetyltransferase
  • CMV, cytomegalovirus
  • DOC, deoxycholic acid
  • HMEC-1, human dermal microvascular endothelial cell line 1
  • HUVEC, human umbilical-vein endothelial cells
  • IκB, inhibitory κB
  • IgκB, immunoglobulin κB
  • IL, interleukin
  • NF-κB, nuclear factor-κB
  • NP40, Nonidet P40
  • TNFα, tumour necrosis factor α
  • TRE, PMA (‘TPA’)-responsive element

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


Journal Title:

Biochemical Journal


Volume 390, Number Pt 1


, Pages 317-324

Type of Work:

Article | Post-print: After Peer Review


In vascular endothelial cells, cytokines induce genes that are expressed in inflammatory lesions partly through the activation of transcription factor NF-κB (nuclear factor-κB). Among the members 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 investigated 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) activated 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 endothelial cells.

Copyright information:

© 2005 Biochemical Society

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