Journal article
Cytomegalovirus modulates transcription factors necessary for the activation of the tumor necrosis factor-alpha promoter
American journal of respiratory cell and molecular biology, Vol.16(1), pp.31-37
01/1997
DOI: 10.1165/ajrcmb.16.1.8998076
PMID: 8998076
Abstract
Several studies have demonstrated that cytomegalovirus (CMV) infection increases expression of the tumor necrosis factor (TNF) gene. This effect is mediated, in part, by an effect of the CMV immediate early 1 (IE1) gene product on the TNF promoter. To further analyze these interactions, we used plasmids with TNF promoter truncations to determine the site within the promoter where the CMV IE1 gene product mediates its effect. The site was localized to a 40-base pair segment that contains a cAMP response element (CREB). Deletion of the cAMP response element increased basal promoter activation but had little effect on IE1-induced activation. Additional studies demonstrated that the cAMP element is flanked 5' by a PU.1 site and 3' by an NF-kappa B site, both of which increase expression of the TNF promoter. These sequences demonstrated IE1 responsiveness. We next determined the relevance of these observations for normal human cells by infecting human alveolar macrophages with CMV. In these studies we evaluated expression of NF-kappa B, PU.1 and CREB by gel shift assay at immediate early times after infection. We found that CMV infection increased the binding activity of NF-kappa B and PU.1 and decreased the binding activity of CREB. CMV infection also increased expression of the TNF gene in alveolar macrophages. These observations suggest that CMV increases TNF gene expression, in part, by altering the binding activity of transcription factors that regulate gene expression.
Details
- Title: Subtitle
- Cytomegalovirus modulates transcription factors necessary for the activation of the tumor necrosis factor-alpha promoter
- Creators
- L J Geist - Department of Medicine, Department of Veterans Affairs, Iowa City, Iowa, USAH A HopkinsL Y DaiB HeM M MonickG W Hunninghake
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.16(1), pp.31-37
- DOI
- 10.1165/ajrcmb.16.1.8998076
- PMID
- 8998076
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Grant note
- HL-3837121 / NHLBI NIH HHS
- Language
- English
- Date published
- 01/1997
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Provost Office Administration; Internal Medicine
- Record Identifier
- 9984213448202771
Metrics
4 Record Views