A novel endothelial-derived anti-inflammatory activity significantly inhibits spontaneous choroidal neovascularisation in a mouse model.
A novel endothelial-derived anti-inflammatory activity significantly inhibits spontaneous choroidal neovascularisation in a mouse model.
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DOI：
10.1186/s13221-016-0036-4
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Ng YS
中科院分区：
文献类型：
--
作者：
Paneghetti L;Ng YS
在血管周围应用时，生长在胶原颗粒上的内皮细胞（EC）可抑制动物模型中的内膜增生，这种作用似乎至少部分是EC衍生的可溶性因子抑制局部血管炎症的结果。为了阐明胶原颗粒上生长的EC的治疗作用的分子基础，表征来自这些细胞的条件培养基的抗炎活性。用肿瘤坏死因子α（TNFα）处理人主动脉内皮细胞（HAEC）和人脐静脉内皮细胞（HUVEC）（染色质免疫沉淀法），并通过分析炎症相关粘附分子E-选择素和血管细胞粘附分子1（VCAM-1）的表达来评价TNF α在胶原颗粒上生长的HAEC产生的条件培养基（ECPCM）中的抗炎作用。使用小鼠品系JR 5558研究了ECPCM的治疗活性，该小鼠品系发展由局部炎症驱动的自发性脉络膜新生血管形成（CNV）病变。ECPCM显著抑制TNFα诱导的E-选择素和VCAM-1的表达。ECPCM不影响这两个基因的mRNA稳定性，但抑制TNFα诱导的NF-κ B转录因子p65亚基与E-选择素和VCAM-1启动子的结合。在体内，全身ECPCM治疗显着减少CNV面积和激活的巨噬细胞的病变募集。负责ECPCM中抗炎活性的分子的表征表明，它不太可能是蛋白质，并且它不是任何更好表征的EC衍生的抗炎分子。由在胶原颗粒上生长的HAEC调节的培养基通过抑制EC中介导炎症反应的基因而表现出显著的抗炎活性。本文的在线版本（doi：10.1186/s13221-016-0036-4）包含补充材料，可供授权用户使用。
Endothelial cells (EC) grown on collagen particles inhibit intimal hyperplasia in animal models when applied perivascularly, and this effect appears to be, at least in part, the result of EC-derived soluble factors that suppress local vascular inflammation. To elucidate the molecular basis of the therapeutic effects of EC grown on collagen particles, the anti-inflammatory activity of conditioned medium from these cells was characterized. Human aortic EC (HAEC) and, for chromatin immunoprecipitation assays, human umbilical vein EC (HUVEC) were treated with tumor necrosis factor alpha (TNFα) in the presence of conditioned medium generated by HAEC grown on collagen particles (ECPCM), and the anti-inflammatory effects were evaluated by analysing the expression of the inflammation-related adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1). The therapeutic activity of ECPCM was studied using the mouse strain JR5558, which develops spontaneous choroidal neovascularisation (CNV) lesions driven by local inflammation. ECPCM significantly suppressed TNFα-induced expression of E-selectin and VCAM-1. ECPCM did not affect the mRNA stability of the two genes, but suppressed TNFα-induced binding of the p65 subunit of NF-kB transcription factor to E-selectin and VCAM-1 promoters. In vivo, systemic ECPCM treatment significantly reduced the CNV area and the recruitment of activated macrophages to the lesions. Characterization of the molecule responsible for the anti-inflammatory activity in ECPCM indicates that it is unlikely to be a protein and that it is not any of the better characterized EC-derived anti-inflammatory molecules. Medium conditioned by HAEC grown on collagen particles exhibits significant anti-inflammatory activity via inhibition of genes that mediate inflammatory responses in EC. The online version of this article (doi:10.1186/s13221-016-0036-4) contains supplementary material, which is available to authorized users.