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Ivy M. Dambuza, Ahjoku Amadi-Obi, Cheng-Rong Yu, Charles E. Egwuagu; IL-27 regulates expression of Complement Factor H in the Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5274.
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Complement Factor H (CFH) is constitutively expressed in the liver and retina by STAT1-dependent mechanisms and dysregulation of CFH expression is associated with Age-related Macular degeneration (AMD). However, mechanism that mediates constitutive expression of CFH in retina is unclear. In this study, we have investigated whether the expression of CFH is regulated by Interleukin-27, an anti-inflammatory cytokine constitutively expressed in retina and known to mediate its effects via STAT1.
Mouse primary retinal cells or human retinal cells were stimulated with IL-27. We investigated the effects of IL-27 on the expression of CFH protein and RNA by Western blotting, RT-PCR analysis and confocal microscopy. We also examined the effects of IL-27 on CFH expression in STAT1-deficient primary retinal cells.
We show that while CFH is expressed in wild type mouse retina its level is markedly reduced in STAT1-deficient retinal cells. We further show that retinal cells responded to IL-27 stimulation by up-regulating expression of CFH through STAT1 and STAT1-inducible transcription factors, interferon regulatory factor-1 (IRF-1) and IRF-8.
Our data showing that IL-27 induced expression of CFH by retinal cells extends its anti-inflammatory functions in the retina and suggests that IL-27 might contribute to mechanisms of ocular immune-privilege by mitigating deleterious effects of complement proteins in retina during inflammation. Our data thus suggest that defects in IL-27 signaling may contribute to defects in CFH expression in patients with AMD.
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