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Title 

NF-κB- and c-Jun-dependent regulation of human cytomegalovirus immediate-early gene enhancer/promoter in response to lipopolysaccharide and bacterial CpG-oligodeoxynucleotides in macrophage cell line RAW 264.7

Authors 

Yong Hee LeeW J SohnD S KimH J Kwon

Publisher 

Federation of European Biochemical Societies

Issue Date 

2004

Citation 

European Journal of Biochemistry, vol. 271, no. 6, pp. 1094-1105

Keywords 

CMV IE gene enhancer/promoterCpG-ODNlipopolysaccharidemacrophageNF-κBbacterium lipopolysaccharideCpG dinucleotidecpg oligodeoxynucleotidedinucleotidegene product

Abstract 

The cytomegalovirus immediate-early (CMV IE) gene enhancer/promoter regulates the expression of immediate-early gene products and initiation of CMV replication. TNF-α and lipopolysaccharide (LPS) strongly activate the promoter, possibly involving NF-κB. CpG-oligodeoxy-nucleotides (CpG-ODNs), which contain unmethylated CpG dinucleotides in the context of particular base sequences, have gained attention because of their stimulating effects, via NF-κB, which have a strong innate immune response. To study the effects of LPS and CpG-ODNs, as well as the mechanisms of their actions regarding CMV IE enhancer/promoter activation, we used a macrophage cell line, RAW 264.7. Stimulation of the cells with LPS or CpG-ODNs resulted in the activation of the CMV IE enhancer/ promoter. We examined the involvement of NF-κB and c-Jun transcription factors by promoter deletion/site-specific mutation analysis and ectopic expression, and found them to have additive effects. Involvement of myeloid differentiation protein, an upstream regulator of NF-κB and c-Jun, was also investigated. Experimental results indicate that both LPS-induced and CpG-ODN-induced activations of CMV IE enhancer/promoter are mediated by Toll-like receptor signaling molecules. Several lines of evidence suggest the potential contribution of bacterial infection in CMV reactivation along with the potential application of CpG-ODNs in gene therapy as a stimulator for the optimal expression of target genes under the control of the CMV IE enhancer/promoter.

ISSN 

0014-2956

Link 

http://dx.doi.org/10.1111/j.1432-1033.2004.04011.x

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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