Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes.
Indoleamine 2,3-dioxygenase (IDO), a flavin-dependent enzyme that catalyzes the conversion of tryptophan to kynurenine, is induced in peripheral blood mononuclear cells by interferon-gamma (IFN gamma). Interleukin-4 (IL-4) is a cytokine that modulates the functional properties of monocytes/macrophages, and we investigated the effects of IL-4 on IDO. We showed that IL-4 inhibited the induction of IDO mRNA and IDO activity by IFN gamma in human monocytes. The inhibitory effect was evident with as little as 2 U/mL of IL-4. These results provide the first evidence that a cytokine can provide a negative signal for IDO expression and that IL-4 can influence the catabolism of tryptophan.
Musso
T
T
Biological Carcinogenesis and Development Program, PRI/DynCorp, Turin, Italy.
Gusella
G L
GL
Brooks
A
A
Longo
D L
DL
Varesio
L
L
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D014364:Tryptophan / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000235:genetics*
D017931:DNA Primers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase