Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy.
Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy.
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DOI：
10.1038/srep28140
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发表时间：
2016-06-17
影响因子：
4.6
通讯作者：
Sonoda KH
中科院分区：
文献类型：
--
作者：
Zhou Y;Yoshida S;Kubo Y;Kobayashi Y;Nakama T;Yamaguchi M;Ishikawa K;Nakao S;Ikeda Y;Ishibashi T;Sonoda KH
缺氧诱导的视网膜新生血管是许多视力威胁疾病的主要病理条件。在本研究中，我们确定了白细胞介素(IL)-12，一种调节血管生成的细胞因子，是否在氧诱导视网膜病变（OIR）小鼠模型中的新生血管形成中起作用。我们发现，与室内空气升高对照组相比，在OIR视网膜中IL-12p35和IL-12p40 mrna的表达均显著降低。IL-12p40敲除（KO）小鼠的无血管区和新生血管簇的大小比野生型（WT）小鼠大。此外，玻璃体内注射重组IL-12可减少无血管区域和新生血管簇。注射IL-12可增强干扰素γ (IFN-γ)及其他下游趋化因子的表达。在体外系统中，IL-12对人视网膜微血管内皮细胞（HRECs）的管状形成无显著影响。此外，阻断IFN-γ可抑制IL-12对病理性新生血管的抑制作用。提示IL-12在抑制病理性视网膜新生血管中起重要作用。
Hypoxia-induced retinal neovascularization is a major pathological condition in many vision-threatening diseases. In the present study, we determined whether interleukin (IL)-12, a cytokine that regulates angiogenesis, plays a role in the neovascularization in a mouse model of oxygen-induced retinopathy (OIR). We found that the expressions of the mRNAs of both IL-12p35 and IL-12p40 were significantly reduced in the OIR retinas compared to that of the room air-raised control. The sizes of the avascular areas and neovascular tufts were larger in IL-12p40 knock-out (KO) mice than that in wild type (WT) mice. In addition, an intravitreal injection of recombinant IL-12 reduced both avascular areas and neovascular tufts. IL-12 injection enhanced the expressions of interferon-gamma (IFN-γ) and other downstream chemokines. In an in vitro system, IL-12 had no significant effect on tube formation of human retinal microvascular endothelial cells (HRECs). Moreover, a blockade of IFN-γ suppressed the inhibitory effect of IL-12 on pathological neovascularization. These results suggest that IL-12 plays important roles in inhibiting pathological retinal neovascularization.