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PMID: 2496143 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Tumor necrosis factor and immune interferon synergistically induce cytochrome b-245 heavy-chain gene expression and nicotinamide-adenine dinucleotide phosphate hydrogenase oxidase in human leukemic myeloid cells.

The Journal of clinical investigation ·Vol. 83 ·No. 5 ·1989-05-00 ·Pages 1570-9

Cassatella MA, Hartman L, Perussia B, Trinchieri G

Abstract

Recombinant tumor necrosis factor (rTNF) and rIFN-gamma induce in the human leukemia cell lines HL-60, ML3, and U937 the accumulation of transcripts of the X chromosome-linked chronic granulomatous disease (X-CGD) gene, encoding the 91-kD heavy chain of cytochrome b-245, a component of the NADPH oxidase of phagocytic cells. The gene is induced within 6 h by either cytokine, and its accumulation is observed upon induction with rIFN-gamma up to 5 d. The combined effect of the two cytokines is more than additive. rIFN-gamma also induces accumulation of X-CGD mRNA in immature myeloid cells from peripheral blood of chronic myeloid leukemia (CML) patients, whereas rTNF has almost no effect. The cells from CML patients constitutively express TNF mRNA, suggesting that endogenously produced TNF may play a role in the effect of rIFN-gamma on these cells. rTNF induces X-CGD gene expression in the myeloid cell lines acting, at least in part, at the transcriptional level, as shown in nuclear run-on experiments. The gene encoding the 22-kD light chain of cytochrome b-245 is constitutively expressed in the human myeloid cell lines and the accumulation of its transcripts is affected by neither rTNF nor rIFN-gamma, rTNF and rIFN-gamma synergistically to induce the cell lines to express the cytochrome b-245 heterodimer (as evaluated by its visible spectrum), and to produce NADPH oxidase activity and H2O2 upon stimulation with phorbol diesters.

MeSH Terms
Cell Line Cytochrome b Group/genetics Drug Synergism Gene Expression Regulation/drug effects Granulomatous Disease, Chronic/enzymology,genetics Humans Interferon-gamma/pharmacology Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics Leukemia, Myeloid/enzymology,genetics,metabolism NADH, NADPH Oxidoreductases/metabolism NADPH Oxidases Oxygen Consumption/drug effects Protein Synthesis Inhibitors/pharmacology Recombinant Proteins Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Cytochrome b Group Protein Synthesis Inhibitors Recombinant Proteins Tumor Necrosis Factor-alpha cytochrome b245 Interferon-gamma NADH, NADPH Oxidoreductases NADPH Oxidases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cassatella M A
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Hartman L
Perussia B
Trinchieri G
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1989-05-00
Pages
1570-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC303863
Subset
IM
Grants
NCI NIH HHS · CA-10815 · United States
NCI NIH HHS · CA-20833 · United States
NCI NIH HHS · CA-32898 · United States
Analysis Services
Analysis Services

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