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Stimulation of B7-H1 in Hepatocarcinoma Cells by Hepatitis B virus X Antigen.
- Source :
-
Immunological Investigations . Sep2010, Vol. 39 Issue 7, p754-769. 16p. 1 Color Photograph, 1 Black and White Photograph, 1 Chart, 3 Graphs. - Publication Year :
- 2010
-
Abstract
- The cross-talk between the hepatitis B virus X protein (HBx) and B7-H1 in hepatocarcinoma (HCC) is unclear. This study analyzed the potential relationships between HBx and B7-H1 in hepatocarcinogenesis. One of human HCC cell lines, HepG2 cells, was transfected to stably express HBx protein (HBx+-HepG2). The transcription of B7-H1 mRNA was increased significantly in these cells compared to cells transfected with control vector (HBx--HepG2), as confirmed by a comparative genome-wide microarray analysis (Capitalbio) and real time quantitative PCR (qPCR). Flow cytometry and western-blot further demonstrated that B7-H1 protein synthesis was enhanced in HBx+-HepG2 cells. Site-directed mutagenesis of promoter constructs revealed that the transcription factor (NF)-κB binding site between 128 and 137 bp upstream of B7-H1 gene transcriptional start site is primarily responsible for HBx-mediated B7-H1 expression. Co-culture experiments with HBx+-HepG2/T cells showed that the number of apoptotic T cells increased profoundly, and this effect could be partially prevented when a neutralizing mAb against B7-H1 was added to the culture, demonstrating that B7-H1 signaling can promote T cell apoptosis. Our results suggest that the expression of B7-H1 in hepatocarcimona cells can be initiated by HBx antigen, thus inducing T cell apoptosis and finally potentially facilitates the genesis of HCC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08820139
- Volume :
- 39
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Immunological Investigations
- Publication Type :
- Academic Journal
- Accession number :
- 53716027
- Full Text :
- https://doi.org/10.3109/08820139.2010.494193