Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
This PDF is available to Subscribers Only