Synergistic effect of interferon-gamma and tumor necrosis factor-alpha on antiviral activity and (2'-5') oligo (A) synthetase induction in a myelomonocytic cell line.
TNF was not observed to have an antiviral effect on either HL60 or U937 cells. However, it did significantly enhance interferon (IFN)-gamma-mediated antiviral activity in U937 cells. Treatment of U937 cells with IFN-gamma enhanced (2'-5') oligo (A) synthetase activity (2.5-fold) but treatment with TNF did not. Combined treatment with TNF-alpha + IFN-gamma increased this activity dramatically (20-40-fold). This increase correlated with the very large increase in the (2'-5') oligo (A) synthetase mRNA level in U937 cells. No such effects were observed in HL60 cells. Furthermore, binding studies and cross-linking analysis showed that IFN-gamma modulated TNF-alpha receptors in U937 cells without altering their properties, but did not do so in HL60 cells.
Wietzerbin
J
J
Unité 196 INSERM, Institut Curie, Paris, France.
Gaudelet
C
C
Catinot
L
L
Chebath
J
J
Falcoff
R
R
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D000998:Antiviral Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015479:Leukemia, Myelomonocytic, Acute / Q000201:enzymology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000998:Antiviral Agents; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase