Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase.
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.
Kuga
S
S
The First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Otsuka
T
T
Niiro
H
H
Nunoi
H
H
Nemoto
Y
Y
Nakano
T
T
Ogo
T
T
Umei
T
T
Niho
Y
Y
D003864:Depression, Chemical; D004790:Enzyme Induction / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D026901:Membrane Transport Proteins; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D009252:NADPH Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; D016753:Interleukin-10; D015847:Interleukin-4; D009247:NADH, NADPH Oxidoreductases; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase