Adenovirus E1A 13S gene product upregulates tumor necrosis factor gene.
Tumor necrosis factor (TNF) is a potential mediator of adenovirus-mediated lung inflammation. I postulated that early genes of adenovirus transactivate the TNF gene as a possible mechanism. To examine this hypothesis, I transfected T-lymphocyte-like Jurkat cells and monocyte/macrophage-like THP-1 cells with plasmids coding for adenovirus E1A 12S or 13S proteins along with a plasmid containing the TNF promoter linked to chloramphenicol acetyltransferase (CAT). In unstimulated Jurkat cells, E1A 13S increased TNF CAT activity 21-fold over cells transfected with control E1A plasmid, whereas 12S had a minimal effect. In unstimulated THP-1 cells, 13S increased TNF CAT activity by almost twofold over cells transfected with the control E1A plasmid; 12S had no effect. The effect of 13S was present in both cell lines when stimulated [Jurkat cells by phorbol 12-myristate 13-acetate; THP-1 cells, by lipopolysaccharide (LPS)]. E1A 13S also increased endogenous TNF mRNA production in LPS-stimulated THP-1 cells. These studies show adenovirus E1A 13S stimulates the TNF gene in inflammatory cell lines.
Metcalf
J P
JP
Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
D017500:Adenovirus E1A Proteins / Q000494:pharmacology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017500:Adenovirus E1A Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate