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C.N. Nagineni, K. Hayashi, B. Detrick, J.J. Hooks; Synergistic Actions of IFN– and TNF–A Induce Secretion of IFN–B by Human Choroidal Fibroblasts but Not by Retinal Pigment Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3348.
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Purpose:The role of interferon–ß (IFN–ß) as an antiviral, anti–inflammatory agent has been reported, and there is an increasing evidence that IFN–ß prevents the breakdown of the blood–tissue barrier by preserving vascular cell and membrane functions. We have studied the role of various cytokines and growth factors in the regulation of IFN–ß expression and secretion by human choroidal fibroblasts (HCF) and human retinal pigment epithelial cells (HRPE). Methods: The primary cultures of HCF and HRPE were prepared from human donor eyes obtained from Eye Banks. HCF and HRPE cultures were treated with cytokines and growth factors for 8 hr and the total RNA prepared was used for conventional and Real Time RT–PCR. Cultures were treated with various agents for 24h, and the secreted IFN–ß protein was determined by ELISA. Results:RT–PCR analyses showed faint bands in HCF treated with IFN–γ or TNF–α. The combination of IFN–γ and TNF–α significantly enhanced IFN–ß mRNA levels. IL–1ß alone or in combination with IFN–γ or TNF–α was not effective in enhancing IFN–ß mRNA in HCF. Growth factors bFGF, PDGF, EGF, IGF–1 and TGF–ß had no effect on IFN–ß mRNA levels. In HRPE, IFN–ß mRNA was not induced by any of the above treatments. The secretion of IFN–ß protein was not detected in HCF treated with various agents except for the combination of IFN–γ and TNF–α (control=0 vs. IFN–γ +TNF–α =18 IU/ml, n–4). In contrast, the secretion of IFN–ß was not detected in HRPE treated with growth factors or cytokines. Conclusions:Our results demonstrate that expression of IFN–ß mRNA and secretion of IFN–ß protein is augmented by the synergistic action of IFN–γ and TNF–α in HCF but not in HRPE. IFN–ß produced by choroidal fibroblasts under inflammatory conditions may act as an anti–inflammatory agent and protect the integrity of the choroidal vasculature and blood–RPE barrier.
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