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

Research output: Contribution to journalArticle

143 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 - 01-04-2006

Fingerprint

Interferon Regulatory Factor-1
STAT1 Transcription Factor
Indoleamine-Pyrrole 2,3,-Dioxygenase
p38 Mitogen-Activated Protein Kinases
Lipopolysaccharides
Cytokines
Interferons
Electrophoretic mobility
Oligonucleotide Probes
Electrophoretic Mobility Shift Assay
Interleukin-1
Cultured Cells
Interleukin-6
Assays
Blood Cells
Blood
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

@article{fcf3473603a741b99b706c38c5ba3249,
title = "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",
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.",
author = "Hidetsugu Fujigaki and Kuniaki Saito and Suwako Fujigaki and Masao Takemura and Kaori Sudo and Hiroshi Ishiguro and Mitsuru Seishima",
year = "2006",
month = "4",
day = "1",
doi = "10.1093/jb/mvj072",
language = "English",
volume = "139",
pages = "655--662",
journal = "Journal of Biochemistry",
issn = "0021-924X",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - 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

T2 - Involvement of p38 mitogen-activated protein kinase and nuclear factor-κB pathways, and synergistic effect of several proinflammatory cytokines

AU - Fujigaki, Hidetsugu

AU - Saito, Kuniaki

AU - Fujigaki, Suwako

AU - Takemura, Masao

AU - Sudo, Kaori

AU - Ishiguro, Hiroshi

AU - Seishima, Mitsuru

PY - 2006/4/1

Y1 - 2006/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33745654304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745654304&partnerID=8YFLogxK

U2 - 10.1093/jb/mvj072

DO - 10.1093/jb/mvj072

M3 - Article

C2 - 16672265

AN - SCOPUS:33745654304

VL - 139

SP - 655

EP - 662

JO - Journal of Biochemistry

JF - Journal of Biochemistry

SN - 0021-924X

IS - 4

ER -