Regulation by endogenous INTERLEUKIN-10 of the expression of nitric oxide synthase induced after ligation of CD23 in human macrophages.
The possible role of interleukin 10 (IL-10) as an endogenous inhibitor of CD23-driven inducible nitric oxide synthase (iNOS) expression in human macrophages was investigated. Cross-linking of CD23 by a monoclonal antibody induced iNOS mRNA, as detected by RT-PCR, and the production of NO measured as the stable derivative, nitrite. A linear correlation was observed between CD23 expression and iNOS activity or NO2- production. The iNOS activity reached a maximum 48 h after ligation of CD23, then declined rapidly until 72 h. In parallel, nitrite production was detected after 24 h and reached a maximum after 48 h. In addition, ligation of the CD23 molecule induced, in a time-dependent manner, the production of IL-10. As this cytokine is known to regulate iNOS induction and activity, we evaluated the effect of a neutralizing mAb to IL-10 on CD23-induced iNOS activity and nitrite production by CD23-bearing macrophages and found that both were significantly enhanced. Furthermore, the addition of exogenous IL-10 suppressed CD23-driven iNOS mRNA expression, iNOS activity and production of nitrite. These data suggest that, after CD23-ligation at the cell surface of human phagocytes, the secretion of IL-10 downregulates the CD23-induced NO production at the transcriptional level, thus providing an efficient feed-back mechanism.
Dugas
N
N
Laboratoire Virus Neurone et Immunité, UFR Kremlin Bicêtre, 94276 Kremlin Bicêtre, France.
Palacios-Calender
M
M
Dugas
B
B
Riveros-Moreno
V
V
Delfraissy
J F
JF
Kolb
J P
JP
Moncada
S
S
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology*; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D009573:Nitrites; D012333:RNA, Messenger; D017455:Receptors, IgE; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II