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Differential regulation of indoleamine 2,3‐dioxygenase by lipopolysaccharide and interferon gamma in murine bone marrow derived dendritic cells
Author(s) -
Jung In Duk,
Lee Chang-Min,
Jeong Young-Il,
Lee Jun Sik,
Park Won Sun,
Han Jin,
Park Yeong-Min
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.02.073
Subject(s) - indoleamine 2,3 dioxygenase , kynurenine , kynurenine pathway , lipopolysaccharide , chemistry , microbiology and biotechnology , signal transduction , interferon gamma , cancer research , ly294002 , biology , immunology , cytokine , tryptophan , pi3k/akt/mtor pathway , biochemistry , amino acid
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‐γ in various cell types and that the induction of IDO can also be mediated through an IFN‐γ‐independent mechanism, these mechanisms still remain unknown. In this study, we investigated whether lipopolysaccharide (LPS) induces the expression of IDO through an IFN‐γ‐mediated signaling pathway or not. IFN‐γ‐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‐γ‐independent mechanism and PI3 kinase and JNK in the LPS‐induced pathway leading to IDO expression.