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Coordinate viral induction of tumor necrosis factor alpha and interferon beta in human B cells and monocytes.

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  • 1. Harvard University, Department of Biochemistry and Molecular Biology, Cambridge, MA 02138.
      Authors
    • Goldfeld AE 1
    (1 author)

Proceedings of the National Academy of Sciences of the United States of America, 01 Mar 1989, 86(5):1490-1494
https://doi.org/10.1073/pnas.86.5.1490 PMID: 2537976 PMCID: PMC286722

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Abstract 

Human tumor necrosis factor alpha (TNF-alpha) gene expression can be induced primarily in cells of the monocyte/macrophage lineage by a variety of inducers, including lipopolysaccharide, phorbol esters such as phorbol 12-myristate 13-acetate, and virus or synthetic double-stranded RNA [poly(I).poly(C)]. In this paper we show that the TNF-alpha gene also responds to virus and phorbol 12-myristate 13-acetate in B lymphocytes and that virus is the most potent inducer of TNF-alpha mRNA in both monocyte and B-cell lines. In addition, we show that viral infection coinduces the expression of TNF-alpha and interferon beta mRNA and that viral induction of both genes is blocked by the kinase inhibitor 2-aminopurine. Inhibition of protein synthesis with cycloheximide had no effect on mRNA expression of the genes in one of three cell lines tested (U937) but blocked the viral induction of both genes in another (Namalwa). Thus, the regulatory factors required for mRNA induction of both genes are present prior to the addition of virus in U937 but not in Namalwa cells. However, in a third cell line (JY), cycloheximide blocked viral induction of the interferon beta gene but not the TNF-alpha gene. Taken together, these observations suggest that viral induction of TNF-alpha and interferon beta gene expression may involve overlapping pathways with both common and distinct regulatory factors.

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Proc Natl Acad Sci U S A. 1989 Mar; 86(5): 1490–1494.
PMCID: PMC286722
PMID: 2537976

Coordinate viral induction of tumor necrosis factor alpha and interferon beta in human B cells and monocytes.

A E Goldfeld and T Maniatis
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Abstract

Human tumor necrosis factor alpha (TNF-alpha) gene expression can be induced primarily in cells of the monocyte/macrophage lineage by a variety of inducers, including lipopolysaccharide, phorbol esters such as phorbol 12-myristate 13-acetate, and virus or synthetic double-stranded RNA [poly(I).poly(C)]. In this paper we show that the TNF-alpha gene also responds to virus and phorbol 12-myristate 13-acetate in B lymphocytes and that virus is the most potent inducer of TNF-alpha mRNA in both monocyte and B-cell lines. In addition, we show that viral infection coinduces the expression of TNF-alpha and interferon beta mRNA and that viral induction of both genes is blocked by the kinase inhibitor 2-aminopurine. Inhibition of protein synthesis with cycloheximide had no effect on mRNA expression of the genes in one of three cell lines tested (U937) but blocked the viral induction of both genes in another (Namalwa). Thus, the regulatory factors required for mRNA induction of both genes are present prior to the addition of virus in U937 but not in Namalwa cells. However, in a third cell line (JY), cycloheximide blocked viral induction of the interferon beta gene but not the TNF-alpha gene. Taken together, these observations suggest that viral induction of TNF-alpha and interferon beta gene expression may involve overlapping pathways with both common and distinct regulatory factors.

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Selected References

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