Differential regulation of indoleamine 2,3-dioxygenase by lipopolysaccharide and interferon gamma in murine bone marrow derived dendritic cells.
Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway, which converts an essential amino acid, L-tryptophan, to N-formylkynurenine. The expression of IDO increases when inflammation is induced by wounding, infection or tumor growth. Although recent studies have suggested that IDO expression is up-regulated by IFN-gamma in various cell types and that the induction of IDO can also be mediated through an IFN-gamma-independent mechanism, these mechanisms still remain unknown. In this study, we investigated whether lipopolysaccharide (LPS) induces the expression of IDO through an IFN-gamma-mediated signaling pathway or not. IFN-gamma-induced expression of IDO expression was inhibited only by JAK inhibitor I. However, LPS-induced expression of IDO was inhibited by LY294002 and SP600125 but not by JAK inhibitor I, SB203580, or U0126. These findings clearly indicate that LPS can induce the IDO expression via an IFN-gamma-independent mechanism and PI3 kinase and JNK in the LPS-induced pathway leading to IDO expression.
Jung
In Duk
ID
Department of Microbiology and Immunology and National Research Laboratory of Dendritic, Cell Differentiation and Regulation, Medical Research Institute, Pusan National University, College of Medicine, Ami-dong 1-10, Seo-gu, Busan 602-739, South Korea.
Lee
Chang-Min
CM
Jeong
Young-Il
YI
Lee
Jun Sik
JS
Park
Won Sun
WS
Han
Jin
J
Park
Yeong-Min
YM
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000201:enzymology; D002070:Butadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D007093:Imidazoles / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology
D000873:Anthracenes; D002070:Butadienes; D002867:Chromones; D007093:Imidazoles; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D053613:Janus Kinase 1; D008070:Lipopolysaccharides; D009025:Morpholines; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C113580:U 0126; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093642:SB 203580