Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase
Kuga, S.; Otsuka, T.; Niiro, H.; Nunoi, H.; Nemoto, Y.; Nakano, T.; Ogo, T.; Umei, T.; Niho, Y.
Experimental Hematology 24(2): 151-157
1996
ISSN/ISBN: 0301-472X PMID: 8641336 Document Number: 456664
Interleukin-10 (IL-10) inhibited the production of superoxide anion (O-2-) 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 b-558 (gp91-phox) and 47-kD cytosolic factor (p47-phox), components of the O-2--generating NADPH oxidase system. Reduction of the mRNAs was distinct within 24 hours. On the other hand, the induced O-2- production by human monocytic leukemia cell lines (THP-1 and HL60) was not inhibited by IL-10. The amount of gp91-phox and p47-phox mRNAs remained unchanged even in the presence of excess amount of IL-10. Taken together, these results suggest that IL-10 inhibits O-2-production by downregulation of the gp91-phox and p47-phox genes in human monocytes.