NMDA-induced interleukin-1β expression is mediated by nuclear factor-kappa B p65 in the retina

Yasushi Kitaoka, Yasunari Munemasa, Toru Nakazawa, Satoki Ueno

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Transcription factors of the nuclear factor-kappa B (NF-κB) p65/RelA may be involved in neuronal cell death. We examined the involvement of NF-κB p65 in N-methyl-d-aspartate (NMDA)-induced upregulation of interleukin (IL)-1β, a proinflammatory cytokine, and subsequent neurotoxicity in the rat retina. Immunohistochemistry showed that IL-1β is localized not only in glial cells, but also in neurons, especially retinal ganglion cells (RGCs) after intravitreal injection of NMDA. Semi-quantitative real-time PCR showed that NMDA induces an increase in IL-1β mRNA levels. Preinjection of NF-κB p65 antisense oligodeoxynucleotide (AS ODN) ameliorated the NMDA-induced increase in IL-1β mRNA expression. Western blot analysis showed elevated levels of retinal IL-1β protein 12 h after intravitreal NMDA injection and this elevation was significantly inhibited by NF-κB p65 AS ODN. Neurotracer labeling showed that the inhibition of NF-κB p65 by AS ODN or siRNA exerted a protective effect against NMDA-induced RGC loss. IL-1β siRNA also had a protective effect on RGC number in NMDA-treated eyes. Penetration of AS ODN and siRNA to cells in the RGC layer and inner nuclear layer was confirmed after labeling with rhodamine or Cy3. These results suggest that NF-κB p65 may participate in the induction of IL-1β expression in NMDA-induced retinal neuronal cell death and that the inhibition of NF-κB p65 and IL-1β with the use of AS ODN or siRNA may be a viable neuroprotective strategy for RGC survival.

Original languageEnglish
Pages (from-to)247-255
Number of pages9
JournalBrain research
Volume1142
Issue number1
DOIs
Publication statusPublished - 2007 Apr 20

Keywords

  • Antisense oligodeoxynucleotide
  • IL-1β
  • N-methyl-d-aspartate
  • Nuclear factor-κB
  • Retina
  • siRNA

ASJC Scopus subject areas

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

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