Abstract
Interleukin-10 (IL-10) inhibited the production of superoxide anion (02-) by both unactivated and interferon-gamma (IFN-gamma)-activated human monocytes. Simultaneous addition of IL-10 with IFN-gamma at the start of incubation was necessary for an optimal inhibitory effect. The degree of inhibition was substantially comparable to that of IL-4, and the combination of suboptimal concentrations of IL-10 and IL-4 produced an additive effect. A similar effect was also obtained when viral IL-10 (vIL-10) was used instead of IL-10. The inhibitory effect of IL-10 was accompanied by the reduced accumulation of transcripts for heavy chain subunit of cytochrome b558 (gp9l-phox) and 47-kD cytosolic factor (p47-phox), components of the O2--generating NADPH oxidase system. Reduction of the mRNAs was distinct within 24 hours. On the other hand, the induced O2- production by human monocytic leukemia cell lines (THP-1 and HL60) was not inhibited by IL-10. The amount of gp9l-phox and p47-phox mRNAs remained unchanged even in the presence of excess amount of IL-1O. Taken together, these results suggest that IL-10 inhibits 02- production by downregulation of the gp9l-phox and p47-phox genes in human monocytes.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Depression, Chemical
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Enzyme Induction / drug effects
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Gene Expression Regulation, Leukemic / drug effects
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HL-60 Cells / drug effects
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HL-60 Cells / metabolism
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Humans
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Interleukin-10 / pharmacology*
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Interleukin-4 / pharmacology
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Leukemia, Myelomonocytic, Acute / genetics
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Leukemia, Myelomonocytic, Acute / pathology
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Leukemia, Promyelocytic, Acute / genetics
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Leukemia, Promyelocytic, Acute / pathology
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Membrane Transport Proteins*
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Monocytes / drug effects*
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Monocytes / metabolism
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NADH, NADPH Oxidoreductases / biosynthesis*
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NADH, NADPH Oxidoreductases / genetics
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NADPH Dehydrogenase / biosynthesis
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NADPH Dehydrogenase / genetics
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NADPH Oxidase 2
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NADPH Oxidases
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Phosphoproteins / biosynthesis*
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Phosphoproteins / genetics
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Recombinant Proteins / pharmacology
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Superoxides / metabolism*
Substances
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Membrane Glycoproteins
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Membrane Transport Proteins
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Neoplasm Proteins
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Phosphoproteins
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RNA, Messenger
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Recombinant Proteins
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neutrophil cytosol factor 67K
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Superoxides
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Interleukin-10
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Interleukin-4
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NADH, NADPH Oxidoreductases
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CYBB protein, human
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NADPH Oxidase 2
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NADPH Oxidases
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CYBA protein, human
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neutrophil cytosolic factor 1
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NADPH Dehydrogenase