Reactive oxygen intermediates cause rapid release of the interleukin-1 decoy receptor from human myelomonocytic cells.
Free radicals play an important role in inflammation. We found that reactive oxygen intermediates (ROI) inhibit interleukin-1beta (IL-1beta) binding on human myelomonocytes. Production of superoxide anion (O2-) by Xanthine (X) and Xanthine-Oxidase (XO) or NADPH caused a reduction (48% +/- 15% in 25 experiments) in the IL-1beta binding of polymorphonuclear cells (PMN) and monocytes that was inhibited by superoxide dismutase (SOD). Hydrogen peroxide (H2O2) was only active on monocytes and this effect was prevented by catalase. O2(-)-induced loss of IL-1beta binding on PMN reached half maximum at 5 minutes and peaked after 30 minutes. The reduction of IL-1beta binding was due to reduction of IL-1beta receptors (R) on PMN surface without any change in affinity. ROI-induced reduction of surface IL-1R was not caused by receptor internalization, but rather by the release of a soluble form (45 kD) of the type II decoy R. The action of ROI on IL-1 binding was selective because major histocompatibility complex class I, CD18 and CD16 were unaffected. The O2(-)-induced release of IL-1 decoy R was not affected by protein synthesis inhibitors, but was partially blocked by protease inhibitors. Release of the IL-1 type II decoy R might represent one mechanism by which ROI antagonize and limit the proinflammatory effects of IL-1.
Sambo
P
P
Istituto de Ricerche Farmacologiche Mario Negri, Milano, Italy.
Fadlon
E J
EJ
Sironi
M
M
Matteucci
C
C
Introna
M
M
Mantovani
A
A
Colotta
F
F
D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000145:classification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D007375:Interleukin-1; D017382:Reactive Oxygen Species; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D014970:Xanthines; D019820:Xanthine; D009249:NADP; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase