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 language | English |
|---|---|
| Pages (from-to) | 655-662 |
| Number of pages | 8 |
| Journal | Journal of Biochemistry |
| Volume | 139 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 01-04-2006 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
Cite this
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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. / Fujigaki, Hidetsugu; Saito, Kuniaki; Fujigaki, Suwako; Takemura, Masao; Sudo, Kaori; Ishiguro, Hiroshi; Seishima, Mitsuru.
In: Journal of Biochemistry, Vol. 139, No. 4, 01.04.2006, p. 655-662.Research output: Contribution to journal › Article
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.
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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 -