白介素38抑制血管增生作用的机理研究

Interleukin 38 (IL-38) inhibits inflammatory responses as an antagonist of IL-36 by binding to IL-36 receptor (IL-36R).IL-38 is a member of the IL-1 family in which IL-1? and IL-18 have the enhancing activity of angiogenesis. However,the role of IL-38 in regulating angiogenesis is poor understood. Our precious study showed that administration of IL-38in vivo inhibited significantly retinal angiogenesis in modelsofoxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV). Furthermore, IL-38 in vitro inhibited significantly the proliferation, scratch wound healing and tube formation of vascular endothelial cells induced by VEGF. Based on these results, this project aimed to elucidatethe mechanisms by which IL-38 inhibits angiogenesis using in vitro model of tube formation, ex vivo model of aortic ring assay induced by VEGF and in vivo models of oxygen-induced retinopathy (OIR), laser-induced choroidal neovascularization(CNV)and Matrigel plug by administration of recombinant IL38.The completion of this project will be to elucidate the role of IL-38 in regulating angiogenesis and provide a theoretical basis for therapeuticsof angiogenesis related diseases.

白介素38（interleukin-38, IL-38）是一新型细胞因子，可与IL-36受体（IL-36R）结合，调节炎症反应。IL-38与具有促血管生成功能的IL-1、IL-18等同为IL-1家族成员，然而IL-38对血管生成的调控作用未有研究涉及。我们在前期工作中发现，IL-38体内注射可显著抑制氧诱导视网膜血管生成模型小鼠（OIR）和激光诱导新生脉络膜血管（Choroidal neovascularization，CNV）模型的视网膜血管增生；IL-38在体外可明显抑制VEGF诱导的血管内皮细胞增殖、划痕愈合和管腔生成。本项目将在原来的基础上，利用离体动脉环血管生成、OIR、CNV模型等手段，从分子、细胞和整体水平深入研究IL-38抑制血管生成分子机制。本项目的完成将为阐明IL-38调控血管生成的机制提供理论依据，为血管生成相关疾病的治疗提供靶点。

白介素 38（interleukin-38, IL-38）是一新型细胞因子，可与 IL-36 受体 （IL-36R）结合，调节炎症反应。IL-38 与具有促血管生成功能的 IL-1、IL-18 等同为 IL-1 家族成员，然而 IL-38 对血管生成的调控作用未有研究涉及。利用氧诱导视网膜血管生成模型小鼠（OIR）模型和体外内皮细胞血管生成实验研究IL-38 对血管生成的作用。体内注射可显著抑制氧诱导视网膜血管生成模型小鼠（OIR）模型的视网膜血管增生；IL-38 在体外可明显抑制 VEGF 诱导的血管内皮细胞增殖、划痕愈合和管腔生成。IL-38 明显抑制血管生成。本项目的结果为阐明 IL-38 调控血管生成的机制提供理论依据，很可能为血管生成相关疾病的治疗提供靶点。