Attenuation of nitric oxide synthase induction in IRF-1-deficient glial cells

Miki Fujimura, Teiji Tominaga, Ichiro Kato, Shin Takasawa, Makoto Kawase, Tadatsugu Taniguchi, Hiroshi Okamoto, Takashi Yoshimoto

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of iNOS, is thought to facilitate neuronal damage during cerebral ischemia. Recently, interferon regulatory factor-1 (IRF-1) has been reported to be an essential transcription factor for iNOS mRNA induction in murine macrophages. However, expression of IRF-1 and its role in the central nervous system have not been examined. In the present study, by using primary glial cell cultures from mice with targeted disruption of the IRF-1 gene, we investigated whether IRF- 1 is involved in iNOS mRNA induction in glial cells. After stimulation with lipopolysaccharide and interferon-γ, IRF-1 mRNA was strongly induced in wild-type (IRF- 1 + / +) glial cells. iNOS mRNA induction and nitrite production in IRF-1 - / - glial cells were reduced as compared with those observed in IRF-1 + / + glial cells. Diethyldithiocarbamate, a selective inhibitor of nuclear transcription factor kappa B (NF-κB) completely inhibited iNOS mRNA induction. These results suggest that not only NF-κB but also IRF-1 play important roles in iNOS mRNA induction in the central nervous system.

Original languageEnglish
Pages (from-to)247-250
Number of pages4
JournalBrain research
Volume759
Issue number2
DOIs
Publication statusPublished - 1997 Jun 6

Keywords

  • Diethyldithiocarbamate
  • Glial cell
  • Inducible nitric oxide synthase
  • Interferon regulatory factor-1
  • Nitric oxide
  • Nuclear transcription factor kappa B

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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