Interleukin 27 Induces the Expression of Complement Factor H (CFH) in the Retina
Interleukin 27 Induces the Expression of Complement Factor H (CFH) in the Retina
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DOI：
10.1371/journal.pone.0045801
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发表时间：
2012-09-20
期刊：
影响因子：
3.7
通讯作者：
Egwuagu, Charles E.
中科院分区：
文献类型：
--
作者：
Amadi-Obi, Ahjoku;Yu, Cheng-Rong;Egwuagu, Charles E.
补体因子H（CFH）是补体系统的中心调节因子，并且与老年性黄斑变性（AMD）的病因学有关，AMD是老年人失明的主要原因。鉴于先前的研究表明视网膜中CFH表达的减少是发展AMD的风险因素，因此对理解视网膜中CFH表达如何调节有很大的兴趣。在这项研究中，我们已经表明，抗炎细胞因子，IL-27，诱导CFH的表达在小鼠视网膜细胞和人视网膜色素上皮细胞（RPE）通过STAT 1介导的上调干扰素调节因子-1（IRF-1）和IRF-8。我们进一步表明，视网膜的神经节和内核层中的细胞组成性地表达IRF-1和IRF-8，并且在眼部炎症期间视网膜中CFH表达的增强与IRF-1、IRF-8和IL-27（IL-27 p28和Ebi 3）表达的显著增加相关。因此，我们的数据揭示了IL-27通过上调CFH在调节补体激活中的新作用，并表明IL-27信号传导或表达的缺陷可能有助于AMD患者视网膜中CFH表达的减少。
Complement factor H (CFH) is a central regulator of the complement system and has been implicated in the etiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. In view of previous studies showing that reduced expression of CFH in the retina is a risk factor for developing AMD, there is significant interest in understanding how CFH expression is regulated in the retina. In this study, we have shown that the anti-inflammatory cytokine, IL-27, induced CFH expression in mouse retinal cells and human retinal pigmented epithelial cells (RPE) through STAT1-mediated up-regulation of Interferon Regulatory Factor-1 (IRF-1) and IRF-8. We further show that cells in the ganglion and inner-nuclear layers of the retina constitutively express IRF-1 and IRF-8 and enhanced CFH expression in the retina during ocular inflammation correlated with significant increase in the expression of IRF-1, IRF-8 and IL-27 (IL-27p28 and Ebi3). Our data thus reveal a novel role of IL-27 in regulating complement activation through up-regulation of CFH and suggest that defects in IL-27 signaling or expression may contribute to the reduction of CFH expression in the retina of patients with AMD.