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An epigenetic mechanism for high, synergistic expression of indoleamine 2,3-dioxygenase 1 (IDO1) by combined treatment with zebularine and IFN-γ: Potential therapeutic use in autoimmune diseases.

Xue, Zhongtian LU ; Sjögren, Hans Olof LU ; Salford, Leif LU and Widegren, Bengt LU (2012) In Molecular Immunology 51(2). p.101-111
Abstract
IDO1 can be induced by interferon gamma (IFN-γ) in multiple cell types. We have earlier described that the DNA methyltransferase inhibitor zebularine also induces IDO1 in several rat cell clones. We now describe a synergistic induction of IDO1 expression by IFN-γ and zebularine. To elucidate the mechanism of the IDO1 induction we have studied the methylation status in the promoter region of the IDO1 gene from both human monocytic THP-1 cells and H1D2 rat colon cancer cells. Interestingly, the IDO1 promoter is hypermethylated and IFN-γ is shown to induce a significant demethylation. The synergism in effect of zebularine and IFN-γ on IDO1 expression is paralleled by a similar synergistic effect on expression of two other IFN-γ-responsive... (More)
IDO1 can be induced by interferon gamma (IFN-γ) in multiple cell types. We have earlier described that the DNA methyltransferase inhibitor zebularine also induces IDO1 in several rat cell clones. We now describe a synergistic induction of IDO1 expression by IFN-γ and zebularine. To elucidate the mechanism of the IDO1 induction we have studied the methylation status in the promoter region of the IDO1 gene from both human monocytic THP-1 cells and H1D2 rat colon cancer cells. Interestingly, the IDO1 promoter is hypermethylated and IFN-γ is shown to induce a significant demethylation. The synergism in effect of zebularine and IFN-γ on IDO1 expression is paralleled by a similar synergistic effect on expression of two other IFN-γ-responsive genes, the transcription factors STAT1 and IRF1 with binding sites in the IDO1 promoter region. The demonstrated synergistic activation of IDO1 expression has implications in relation to therapeutic induction of immunosuppression in autoimmunity and chronic inflammation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Human and rat, IDO1 gene promoter, DNA methylation, Zebularine, IFN-gamma, Transcription factors
in
Molecular Immunology
volume
51
issue
2
pages
101 - 111
publisher
Pergamon
external identifiers
  • wos:000304687500001
  • pmid:22424783
  • scopus:84860360467
ISSN
1872-9142
DOI
10.1016/j.molimm.2012.01.006
language
English
LU publication?
yes
id
3c992f82-6179-4f36-9f7c-722721c6fa57 (old id 2431704)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22424783?dopt=Abstract
date added to LUP
2012-04-03 11:15:39
date last changed
2017-11-19 03:08:18
@article{3c992f82-6179-4f36-9f7c-722721c6fa57,
  abstract     = {IDO1 can be induced by interferon gamma (IFN-γ) in multiple cell types. We have earlier described that the DNA methyltransferase inhibitor zebularine also induces IDO1 in several rat cell clones. We now describe a synergistic induction of IDO1 expression by IFN-γ and zebularine. To elucidate the mechanism of the IDO1 induction we have studied the methylation status in the promoter region of the IDO1 gene from both human monocytic THP-1 cells and H1D2 rat colon cancer cells. Interestingly, the IDO1 promoter is hypermethylated and IFN-γ is shown to induce a significant demethylation. The synergism in effect of zebularine and IFN-γ on IDO1 expression is paralleled by a similar synergistic effect on expression of two other IFN-γ-responsive genes, the transcription factors STAT1 and IRF1 with binding sites in the IDO1 promoter region. The demonstrated synergistic activation of IDO1 expression has implications in relation to therapeutic induction of immunosuppression in autoimmunity and chronic inflammation.},
  author       = {Xue, Zhongtian and Sjögren, Hans Olof and Salford, Leif and Widegren, Bengt},
  issn         = {1872-9142},
  keyword      = {Human and rat,IDO1 gene promoter,DNA methylation,Zebularine,IFN-gamma,Transcription factors},
  language     = {eng},
  number       = {2},
  pages        = {101--111},
  publisher    = {Pergamon},
  series       = {Molecular Immunology},
  title        = {An epigenetic mechanism for high, synergistic expression of indoleamine 2,3-dioxygenase 1 (IDO1) by combined treatment with zebularine and IFN-γ: Potential therapeutic use in autoimmune diseases.},
  url          = {http://dx.doi.org/10.1016/j.molimm.2012.01.006},
  volume       = {51},
  year         = {2012},
}