The signal transducer and activator of transcription 1α and interferon regulatory factor 1 are not essential for the induction of indoleamine 2,3-dioxygenase by lipopolysaccharide: Involvement of p38 mitogen-activated protein kinase and nuclear factor-κB pathways, and synergistic effect of several proinflammatory cytokines

Hidetsugu Fujigaki, Kuniaki Saito, Suwako Fujigaki, Masao Takemura, Kaori Sudo, Hiroshi Ishiguro, Mitsuru Seishima

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151 Citations (Scopus)

Abstract

Indoleamine 2,3-dioxygenase (IDO) is induced by interferon (IFN)-γ-mediated effects of the signal transducer and activator of transcription 1α (STAT1α) and interferon regulatory factor (IRF)-1. The induction of IDO can also be mediated through an IFN-γ-independent mechanism, although the mechanism of induction has not been identified. In this study, we explored whether lipopolysaccharide (LPS) or several proinflammatory cytokines can induce IDO via an IFN-γ-independent mechanism, and whether IDO induction by LPS requires the STAT1α and IRF-1 signaling pathways. IDO was induced by LPS or IFN-γ in peripheral blood mononuclear cells and THP-1 cells, and a synergistic IDO induction occurred when TBP-1 cells were cultured in the presence of a combination of tumor necrosis factor-α, interleukin-6 or interleukin-1β. An electrophoretic mobility shift assay using STAT1α and IRF-1 consensus oligonucleotide probes showed no STAT1α or IRF-1 binding activities in LPS-stimulated THP-1 cells. Further, the LPS-induced IDO activity was inhibited by both p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) inhibitors. These findings suggest that the induction of IDO by LPS in THP-1 cells is not regulated by IFN-γ via recruitment of STAT1α or IRF-1 to the intracellular signaling pathway, and may be related to the activity of the p38 MAPK pathway and NF-κB.

Original languageEnglish
Pages (from-to)655-662
Number of pages8
JournalJournal of Biochemistry
Volume139
Issue number4
DOIs
Publication statusPublished - 04-2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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