Nuclear factor-κB p65 and upregulation of interleukin-6 in retinal ischemia/reperfusion injury in rats

Nuclear factor-κB p65 and upregulation of interleukin-6 in retinal ischemia/reperfusion injury... We previously demonstrated that endogenous interleukin-6 (IL-6) is upregulated and may be neuroprotective after retinal ischemia. The purpose of this study is to investigate the role of nuclear factor kappa-B (NF-κB) in regulating IL-6 expression after ischemia. NF-κB p65 mRNA levels were significantly elevated between 2 and 12 h after the insult. A high number of NF-κB p65 positive cells were detected in the inner retina at 12 h after ischemia. Activated nuclear NF-κB p65 and IL-6 were colocalized in cells, which were also marked by a microglial/phagocytic cell marker (ED1) in the inner retina. Carbobenzoxy- l -leucyl- l -leucyl- l -leucinal (MG-132, a proteasome inhibitor, which inhibits IκB degradation and hence prevents the activation and translocation of NF-κB into the nucleus) abolished the increase in NF-κB p65 mRNA levels after the insult, while there was no effect by helenalin (an inhibitor which inhibits NF-κB activity by alkylation of the p65 subunit, thereby blocking its binding to the target DNA). However, MG-132 and/or helenalin significantly diminished the increase in IL-6 mRNA levels after the insult. Small interfering RNAs (siRNAs, inhibit target gene expression through the sequence-specific destruction of the target messenger RNA) against NF-κB p65 significantly reduced the increase in NF-κB p65 mRNA levels as well as IL-6 mRNA levels after ischemia. The number of retinal ganglion cells (RGCs) was also significantly decreased using the inhibitors of NF-κB compared with those of the controls after ischemia. These findings support the hypothesis that upregulation of endogenous retinal IL-6 in retinal I/R injury in microglial/phagocytic cells is controlled predominantly by NF-κB p65. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Nuclear factor-κB p65 and upregulation of interleukin-6 in retinal ischemia/reperfusion injury in rats

Loading next page...
 
/lp/elsevier/nuclear-factor-b-p65-and-upregulation-of-interleukin-6-in-retinal-1xI2YvbJ0U
Publisher site
See Article on Publisher Site

Abstract

We previously demonstrated that endogenous interleukin-6 (IL-6) is upregulated and may be neuroprotective after retinal ischemia. The purpose of this study is to investigate the role of nuclear factor kappa-B (NF-κB) in regulating IL-6 expression after ischemia. NF-κB p65 mRNA levels were significantly elevated between 2 and 12 h after the insult. A high number of NF-κB p65 positive cells were detected in the inner retina at 12 h after ischemia. Activated nuclear NF-κB p65 and IL-6 were colocalized in cells, which were also marked by a microglial/phagocytic cell marker (ED1) in the inner retina. Carbobenzoxy- l -leucyl- l -leucyl- l -leucinal (MG-132, a proteasome inhibitor, which inhibits IκB degradation and hence prevents the activation and translocation of NF-κB into the nucleus) abolished the increase in NF-κB p65 mRNA levels after the insult, while there was no effect by helenalin (an inhibitor which inhibits NF-κB activity by alkylation of the p65 subunit, thereby blocking its binding to the target DNA). However, MG-132 and/or helenalin significantly diminished the increase in IL-6 mRNA levels after the insult. Small interfering RNAs (siRNAs, inhibit target gene expression through the sequence-specific destruction of the target messenger RNA) against NF-κB p65 significantly reduced the increase in NF-κB p65 mRNA levels as well as IL-6 mRNA levels after ischemia. The number of retinal ganglion cells (RGCs) was also significantly decreased using the inhibitors of NF-κB compared with those of the controls after ischemia. These findings support the hypothesis that upregulation of endogenous retinal IL-6 in retinal I/R injury in microglial/phagocytic cells is controlled predominantly by NF-κB p65.

Journal

Brain ResearchElsevier

Published: Apr 7, 2006

References

  • Focal ischemia induces transient expression of IL-6 in the substantia nigra pars reticulata
    Dihne, M.; Block, F.
  • Physiological and pathological roles of interleukin-6 in the central nervous system
    Gruol, D.L.; Nelson, T.E.
  • Neuroprotective effects of interleukin-6 on NMDA-induced rat retinal damage
    Inomata, Y.; Hirata, A.; Yonemura, N.; Koga, T.; Kido, N.; Tanihara, H.
  • Interleukin-6 protects cultured cerebellar granule neurons against glutamate-induced neurotoxicity
    Peng, Y.P.; Qiu, Y.H.; Lu, J.H.; Wang, J.J.
  • Interleukin-6 in retinal ischemia reperfusion injury in rat
    Sanchez, R.N.; Chan, C.K.; Garg, S.; Kwong, J.M.; Wong, M.J.; Sadun, A.A.; Lam, T.T.
  • Cerebral neurons expression interleukin-6 after transient forebrain ischemia in gerbils
    Suzuki, S.; Tanaka, K.; Nagata, E.; Ito, D.; Dembo, T.; Fukuuchi, Y.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off