In:
European Journal of Biochemistry, Wiley, Vol. 271, No. 6 ( 2004-03), p. 1094-1105
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‐oligodeoxynucleotides (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.
Type of Medium:
Online Resource
ISSN:
0014-2956
,
1432-1033
DOI:
10.1111/ejb.2004.271.issue-6
DOI:
10.1111/j.1432-1033.2004.04011.x
Language:
English
Publisher:
Wiley
Publication Date:
2004
detail.hit.zdb_id:
1398347-7
detail.hit.zdb_id:
2172518-4
SSG:
12