April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Synthetic Tellurium Compound, AS101, Down-regulates Proinflammatory Molecules In Retinal Pigment Epithelium
Author Affiliations & Notes
  • Diamond Ling
    Laboratory of Immunology, NEI, Bethesda, Maryland
  • Baoying Liu
    Laboratory of Immunology, NEI, Bethesda, Maryland
  • Zhiyu Li
    Laboratory of Immunology, NEI, Bethesda, Maryland
  • Jia Ni
    Laboratory of Immunology, NEI, Bethesda, Maryland
  • Benjamin Sredni
    C.A.I.R. Institute, Bar-Ilan University, Ramat Gan 52900, Israel
  • Robert B. Nussenblatt
    Laboratory of Immunology, NEI, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  Diamond Ling, None; Baoying Liu, None; Zhiyu Li, None; Jia Ni, None; Benjamin Sredni, BioMAS (P); Robert B. Nussenblatt, BioMAS (F)
  • Footnotes
    Support  NIH Intramural Research Program
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4299. doi:
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      Diamond Ling, Baoying Liu, Zhiyu Li, Jia Ni, Benjamin Sredni, Robert B. Nussenblatt; Synthetic Tellurium Compound, AS101, Down-regulates Proinflammatory Molecules In Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4299.

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

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Purpose: : AS101, a nontoxic organotellurium compound, exhibits immunomodulating activity in vivo and in vitro. It is purported to regulate proinflammatory cytokines, such as IL-1β. Many such cytokines are known to stimulate production of proinflammatory cytokines/chemokines, such as IL-6, IL-8 and MCP-1, which are secreted by the retinal pigment epithelium (RPE). The goal of this study is to analyze AS101’s effects on cytokine-induced cytokine/chemokine secretion in human RPE in vitro.

Methods: : Primary human RPE cells and a transformed human RPE cell line, ARPE 19, were treated with AS101 at various concentrations and then co-cultured with or without TNFα, IL-1β, IFNγ, or a combined "proinflammatory cytokine cocktail". After 24 or 48 hours, supernatants and cells were collected. Real-time polymerase chain reactions (RT-PCR) were used to detect mRNA expression of IL-6, IL-8, and MCP-1.

Results: : AS101 decreases IL-6, IL-8, and MCP-1 mRNA expression levels in RPE cells cultured without cytokines. The proinflammatory cocktail substantially increases IL-6 and IL-8 mRNA levels, and more modestly increases MCP-1 mRNA levels in primary RPE and ARPE19 cells after 24 and 48 hours of co-culture. However, AS101 dramatically suppresses the elevation of all three cytokine/chemokine mRNA levels in a dose-dependent manner. AS101 also inhibits these three cytokine/chemokine mRNA expression in cells cultured individually with IL-1β and to a lesser extent, TNFα.

Conclusions: : AS101 exhibits anti-inflammatory effects on human RPE cells by suppressing production of purported proinflammatory moleculess IL-6, IL-8 and MCP-1. Importantly, proinflammatory cytokine-induced production of these molecules is also inhibited by AS101. Our data suggests AS101 may have clinical potential in the treatment of inflammatory eye diseases.

Keywords: cytokines/chemokines • retinal pigment epithelium • drug toxicity/drug effects 

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