April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Celastrol Modulates inflammatory Responses in Retinal Pigment Epithelial Cells (RPE)
Author Affiliations & Notes
  • Qingning Bian
    Human Nutrition Res Ctr on Aging, Tufts University, Boston, Massachusetts
  • Tingyu Qin
    Human Nutrition Res Ctr on Aging, Tufts University, Boston, Massachusetts
  • Fu Shang
    Human Nutrition Res Ctr on Aging, Tufts University, Boston, Massachusetts
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6584. doi:
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      Qingning Bian, Tingyu Qin, Fu Shang; Celastrol Modulates inflammatory Responses in Retinal Pigment Epithelial Cells (RPE). Invest. Ophthalmol. Vis. Sci. 2011;52(14):6584.

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Abstract

Purpose: : Emerging evidence suggests that inflammation is closely related to age-related macular degeneration (AMD) and RPE is a primary ocular source of inflammatory cytokines. The aim of this study was to investigate the effects of celastrol, a pentacyclic-triterpene, on expression and secretion of inflammatory cytokines from cultured RPE (ARPE-19).

Methods: : Confluent ARPE-19 were treated with 0.05-10 µM celastrol for 6 h. The mRNA levels of inflammatory cytokines were determined by Real-Time PCR. Protein levels of these cytokines were determined by enzyme-linked immunosorbent assay. Anti-inflammatory effects of celastrol were also evaluated in the presence of lipopolysaccharide (LPS) -stimulation or upon proteasome inhibition.

Results: : Treatment of the APRE-19 cells with celastrol suppressed the production of inflammatory cytokines, such as Il-6, IL-8 and MCP-1. The suppressive effects were dose-dependent. The maximal suppressive effects were obtained at a concentration of 0.5 µM celastrol in the cell culture medium. When treated with 0.5 µM celastrol, mRNA levels of IL-6, IL-8 and MCP-1 decreased 40-90%, and protein levels decreased 20-50%. Further increases in celastrol concentrations reduced the suppressive effects. LPS-stimulation (0.5 µg/ml) increased the production of IL-6 IL-8 and MCP-1 by 2-3 fold. Treatment of the cells with 0.1-0.5 µM celastrol suppressed the LPS- induced production of these inflammatory cytokines by as much as 90%. As shown previously, prolonged proteasome inhibition (10 µM MG132 for 8 h) up-regulated the production of IL-8 by ARPE-19. Treatment of the cells with 0.1-0.5 µM celastrol also suppressed proteasome inhibition-induced IL-8 production.

Conclusions: : Our data suggest that celastrol suppresses the production of inflammatory cytokines by RPE. Thus, celastrol appears to be a potential drug candidate for treatment of ocular inflammation and related eye diseases, such as AMD.

Keywords: gene/expression • age-related macular degeneration • inflammation 
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