TY - JOUR
T1 - NMDA-induced interleukin-1β expression is mediated by nuclear factor-kappa B p65 in the retina
AU - Kitaoka, Yasushi
AU - Munemasa, Yasunari
AU - Nakazawa, Toru
AU - Ueno, Satoki
N1 - Funding Information:
This work was supported by Grant-in-Aid No. 18791303 (Y.K.) from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government.
PY - 2007/4/20
Y1 - 2007/4/20
N2 - 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.
AB - 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.
KW - Antisense oligodeoxynucleotide
KW - IL-1β
KW - N-methyl-d-aspartate
KW - Nuclear factor-κB
KW - Retina
KW - siRNA
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U2 - 10.1016/j.brainres.2007.01.097
DO - 10.1016/j.brainres.2007.01.097
M3 - Article
C2 - 17320050
AN - SCOPUS:33947285383
VL - 1142
SP - 247
EP - 255
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1
ER -