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Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells.

Publication ,  Journal Article
Shu, HB; Agranoff, AB; Nabel, EG; Leung, K; Duckett, CS; Neish, AS; Collins, T; Nabel, GJ
Published in: Mol Cell Biol
October 1993

Vascular cell adhesion molecule 1 (VCAM-1) is expressed in both endothelial and epithelial cell types, where it contributes to lymphocyte migration to sites of inflammation. Its expression is regulated by cytokines, in part through two kappa B-like regulatory elements. Because NF-kappa B can be composed of multiple alternative subunits with differential effects on gene expression, the role of different specific NF-kappa B family members subunits in VCAM-1 regulation is unknown. In this report, we define the contribution of different NF-kappa B family members to VCAM-1 gene regulation. We show that both kappa B sites in the VCAM-1 enhancer are required to optimally stimulate gene expression, but the enhancer is differentially regulated by specific combinations of NF-kappa B subunits. At low concentrations, RelA(p65) acted in concert with the approximately 50-kDa product of p105 NF-kappa B, NF-kappa B1(p50), to stimulate transcription, and at high concentrations, RelA(p65) alone stimulated the VCAM-1 promoter. In contrast, NF-kappa B2 inhibited functional activation of the VCAM reporter by p65. Consistent with this finding, an additional binding complex was detected by using recombinant NF-kappa B2(p49)/RelA(p65) with radiolabeled VCAM kappa B site probes. Interestingly, the human immunodeficiency virus enhancer responded differently to stimulation by NF-kappa B subunits, with optimal response to p49(100)/p65. Analysis of NF-kappa B mRNA in human umbilical vein endothelial cells revealed that nfkb1, nfkb2, and relA NF-kappa B but not c-rel were induced by tumor necrosis factor alpha and lipopolysaccharide, which also induce VCAM-1. These data suggest that specific subunits of NF-kappa B regulate VCAM-1 and differentially activate other genes in these cells.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

October 1993

Volume

13

Issue

10

Start / End Page

6283 / 6289

Location

United States

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha
  • Transfection
  • Transcription Factors
  • Swine
  • Proto-Oncogene Proteins
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
  • Molecular Sequence Data
  • Lipopolysaccharides
 

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Shu, H. B., Agranoff, A. B., Nabel, E. G., Leung, K., Duckett, C. S., Neish, A. S., … Nabel, G. J. (1993). Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells. Mol Cell Biol, 13(10), 6283–6289. https://doi.org/10.1128/mcb.13.10.6283-6289.1993
Shu, H. B., A. B. Agranoff, E. G. Nabel, K. Leung, C. S. Duckett, A. S. Neish, T. Collins, and G. J. Nabel. “Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells.Mol Cell Biol 13, no. 10 (October 1993): 6283–89. https://doi.org/10.1128/mcb.13.10.6283-6289.1993.
Shu HB, Agranoff AB, Nabel EG, Leung K, Duckett CS, Neish AS, et al. Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells. Mol Cell Biol. 1993 Oct;13(10):6283–9.
Shu, H. B., et al. “Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells.Mol Cell Biol, vol. 13, no. 10, Oct. 1993, pp. 6283–89. Pubmed, doi:10.1128/mcb.13.10.6283-6289.1993.
Shu HB, Agranoff AB, Nabel EG, Leung K, Duckett CS, Neish AS, Collins T, Nabel GJ. Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells. Mol Cell Biol. 1993 Oct;13(10):6283–6289.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

October 1993

Volume

13

Issue

10

Start / End Page

6283 / 6289

Location

United States

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha
  • Transfection
  • Transcription Factors
  • Swine
  • Proto-Oncogene Proteins
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
  • Molecular Sequence Data
  • Lipopolysaccharides