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. 1991 May 25;19(10):2645–2653. doi: 10.1093/nar/19.10.2645

An NF kappa B-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription.

J Whelan 1, P Ghersa 1, R Hooft van Huijsduijnen 1, J Gray 1, G Chandra 1, F Talabot 1, J F DeLamarter 1
PMCID: PMC328182  PMID: 1710341

Abstract

The endothelial leukocyte adhesion molecule 1 (ELAM-1) is transiently expressed specifically on the surface of cytokine-induced endothelial cells. We demonstrate that the transient expression of the protein is paralleled by an increase and decrease in transcription of the ELAM-1 gene. To identify the cis-acting transcription control regions within the ELAM-1 gene that are responsible for this cytokine-induced expression, we isolated and analyzed an ELAM-1 genomic clone containing sequences upstream of the transcription start site. We constructed a series of ELAM-1 deletion mutants linked to a reporter gene and analyzed their expression in both endothelial and non-endothelial cells. Results show that a fragment of 233 bp upstream of the transcription start site is sufficient to confer cytokine inducibility upon the reporter gene in both endothelial and non-endothelial cells. Further analysis defined two elements within this region that are involved in the cytokine inducibility of the ELAM-1 gene. One element lies within the -233 to -117 region, the other element represents an NF kappa B consensus binding site between nucleotides -94 to -85. Gel shift analysis reveals increased binding of an NF kappa B-like factor to this consensus sequence in extracts prepared from IL-1-induced endothelial cells. The results suggest that cytokine induction of ELAM-1 gene transcription is imparted by a combination of positive factors, one being an NF kappa B-like transcription factor, interacting with cis-acting elements within the enhancer/promoter of the gene.

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Selected References

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