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.