Autocrine secretion of tumor necrosis factor under the influence of interferon-. gamma. amplifies HLA-DR gene induction in human monocytes
- Institut Pasteur, Paris (France)
Recombinant interferon-{gamma} (IFN-{gamma}) induced HLA-DR gene expression in both U937 and THP-1 human monocytic cell lines, although the former was only very weakly inducible. Combination of recombinant tumor necrosis factor (TNF) and IFN-{gamma} resulted in a synergistic enhancement of DR mRNA and protein induction in both cell lines. TNF alone increased the constitutive expression of the DR gene in THP-1 cells. In the HLA class II-negative U937 cells, TNF used alone was not able to induce DR gene expression. Such a negative result was not due to a lack of TNF receptor expression in U937 cells, since TNF clearly induced HLA class I and TNF gene expression in this cell line. THP-1, but not U937, cells secreted TNF under the influence of IFN-{gamma}. Neutralization of TNF by a specific antibody decreased IFN-{gamma}-induced DR antigen expression in THP-1 cultures. These observations indicate that TNF is not able to directly induce DR gene expression, but rather amplifies ongoing expression of this gene, whether constitutive or induced by IFN-{gamma}. In the two cell lines tested, the level of DR inducibility under the influence of IFN-{gamma} used alone depended on a different inducibility of TNF secretion by IFN-{gamma}. Altogether, the observations indicate that TNF, whether exogenous or endogenously produced under the influence of IFN-{gamma}, amplifies DR gene expression in monocytes, a phenomenon that may provide to such antigen-presenting cells a selective sensitivity to the DR-inducing effects of IFN-{gamma}.
- OSTI ID:
- 5641933
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:16; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
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GENES
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LEUKOCYTES
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LYMPHOKINES
MAMMALS
MAN
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