June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Resveratrol Attenuates Priming of the NLRP3 Inflammasome by Hydrogen Peroxide
Author Affiliations & Notes
  • Scott Lallier
    Duke University School of Medicine, Durham, North Carolina, United States
  • Nicholas Anthony Besley
    Duke University School of Medicine, Durham, North Carolina, United States
  • Ping Yang
    Duke University School of Medicine, Durham, North Carolina, United States
  • Glenn J Jaffe
    Duke University School of Medicine, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Scott Lallier, None; Nicholas Besley, None; Ping Yang, None; Glenn Jaffe, None
  • Footnotes
    Support  : This work was supported, in part, by Unrestricted Research to Prevent Blindness Grant and the NIH Core Grant [P30EY005722].
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2704. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Scott Lallier, Nicholas Anthony Besley, Ping Yang, Glenn J Jaffe; Resveratrol Attenuates Priming of the NLRP3 Inflammasome by Hydrogen Peroxide. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2704.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : The NLRP3 inflammasome has been implicated in the pathogenesis of age-related macular degeneration (AMD). It has been previously suggested that reactive oxygen species can prime the NLRP3 inflammasome and induce inflammatory cytokine expression. We and others have shown that resveratrol decreases oxidant injury in RPE cells. However, the effect of resveratrol on oxidant-induced inflammasome priming and inflammatory expression in RPE cells has not been well established. Here we test hydrogen peroxide’s (H2O2) ability to prime the inflammasome and induce inflammatory gene expression in cultured human retinal pigment epithelial (RPE) cells. We hypothesized that H2O2 would prime the inflammasome, induce inflammatory gene expression, and that resveratrol would protect against these effects.

Methods : Cultured human RPE cells were treated with 30 µM resveratrol for 2.5 hours, followed by treatment with 700 µM hydrogen peroxide in the presence or absence of 30 µM resveratrol for 2.5 or 4 hours as indicated. Phosphorylation of Nuclear Factor Kappa B (NF-κB) was evaluated using western blot. Inflammasome and classic inflammatory gene expression was measured with qPCR.

Results : H2O2 treatment resulted in a 4-fold increase (p<.05) in phosphorylation of NF-κB as determined by western blot. H2O2 treatment resulted in an 18-fold increase in NLRP3 (p<.05), 1.8-fold increase in IL-1β (p <.05), and 2.4-fold increase in IL-8 (p <.05) at determined by qPCR. Resveratrol protected against the upregulation of NLRP3 (p <.05) and IL-1beta (p <.05) by H2O2. Resveratrol did not significantly reduce IL-8 expression. Under these experimental conditions, no increase was observed in IL-6, MCP-1, or CXCL1 gene expression.

Conclusions : H2O2 primes the human RPE cell NLRP3 inflammasome and upregulates inflammasome-associated cytokines. These effects were blocked by resveratrol. Further studies are needed to determine if other oxidants prime the RPE cell inflammasome, and the mechanism by which resveratrol exerts its inhibitory effect. These studies will add to our understanding of the pathogenesis of AMD and possible preventive strategies.

This is a 2021 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×