Interleukin-15 inhibits sodium nitroprusside-induced apoptosis of synovial fibroblasts and vascular endothelial cells.
Interleukin-15 inhibits sodium nitroprusside-induced apoptosis of synovial fibroblasts and vascular endothelial cells.
复制标题
Interleukin-15 抑制硝普钠诱导的滑膜成纤维细胞和血管内皮细胞凋亡。
DOI：
10.1002/art.10610
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Grom,AlexeiA
中科院分区：
文献类型：
--
作者：
Yang,Lin;Thornton,Sherry;Grom,AlexeiA
目的幼年类风湿性关节炎（JRA）的病理特征之一是炎症滑膜组织或血管翳的肿瘤样扩张，这会导致该疾病的大部分关节损伤。血管翳的扩张由新血管的广泛形成支持。我们之前已经表明，移植到SCID小鼠中的切碎的JRA滑膜组织的血运重建与组织中的炎症活性强度和白细胞介素-15（IL-15）表达相关。由于滑膜血管内皮细胞（VEC）表达IL-15受体，本研究进行调查的假设，IL-15可能发挥作用，在新生血管的血管翳。MethodsTo评估IL-15可能的血管生成活性，我们评估了重组人IL-15（rHuIL-15）的能力，直接诱导VEC生长和刺激滑膜细胞产生内皮生长因子。由于IL-15已被证明可以抑制某些免疫细胞的凋亡，因此我们也对它是否可能对VEC具有类似的作用感兴趣。细胞凋亡诱导硝普钠（SNP）在1-2 mM加入到>80%汇合的原代VECs，和凋亡细胞的数量通过annexin V assay. Results 10-100 ng/ml的rHuIL-15加入到原代滑膜成纤维细胞培养未能上调这些细胞的血管内皮生长因子和血管生成素1的表达。虽然rHuIL-15未能诱导VEC的促有丝分裂反应，但它促进了这些细胞在Matrigel上的存活。50 ng/ml rHuIL-15预孵育VECs可显著降低VECs发生凋亡的比例。结论IL-15可促进VECs在Matrigel上的存活，并抑制SNP诱导的内皮细胞凋亡。我们推测这种机制可能与JRA滑膜中新形成的血管结构的稳定有关。
ObjectiveOne of the pathologic hallmarks of juvenile rheumatoid arthritis (JRA) is a tumor‐like expansion of inflamed synovial tissue, or pannus, which causes much of the joint damage in this disease. The expansion of pannus is supported by extensive formation of new blood vessels. We have previously shown that revascularization of minced JRA synovial tissues engrafted into SCID mice correlated with the intensity of inflammatory activity in the tissues and with interleukin‐15 (IL‐15) expression. Since synovial vascular endothelial cells (VECs) expressed IL‐15 receptors, the present study was undertaken to investigate the hypothesis that IL‐15 might play a role in neovascularization of the pannus.MethodsTo evaluate IL‐15 for possible angiogenic activity, we assessed the ability of recombinant human IL‐15 (rHuIL‐15) to induce VEC growth directly and to stimulate synovial cells to produce endothelial growth factors. Since IL‐15 had been shown to inhibit apoptosis of certain immune cells, we were also interested in whether it might have similar effects on VECs. Apoptosis was induced by addition of sodium nitroprusside (SNP) at 1–2 mMto >80% confluent primary VECs, and numbers of apoptotic cells were determined by annexin V assay.ResultsAddition of rHuIL‐15 at 10–100 ng/ml to primary synovial fibroblast cultures failed to up‐regulate expression of vascular endothelial growth factor and angiopoietin 1 by these cells. Although rHuIL‐15 failed to induce a mitogenic response of VECs, it promoted survival of these cells on Matrigel. Preincubation of VECs with rHuIL‐15 at 50 ng/ml significantly reduced the proportion of VECs undergoing apoptosis.ConclusionIL‐15 promotes survival of VECs on Matrigel and inhibits SNP‐induced apoptosis of endothelial cells. We hypothesize that this mechanism may be relevant to the stabilization of newly formed vascular structures in JRA synovium.
登录
查看更多内容
影响因子：
15.9
作者：
Blair, RJ;Meng, H;Gruber, BL
通讯作者：
Gruber, BL
幼年类风湿性关节炎滑膜组织中干扰素-γ：白细胞介素 4 的比率和相关 1 型细胞因子的表达。
DOI：
--
发表时间：
2002
期刊：
The Journal of rheumatology.
影响因子：
--
作者：
Scola,MichaelP;Thompson,SusanD;Brunner,HermineI;Tsoras,MonicaK;Witte,David;VanDijk,MarcA;Grom,AlexeiA;Passo,MurrayH;Glass,DavidN
通讯作者：
Glass,DavidN
影响因子：
--
作者：
CASSIDY, JT;LEVINSON, JE;YOUNG, D
通讯作者：
YOUNG, D
影响因子：
15.9
作者：
Oppenheimer-Marks, N;Brezinschek, RI;Lipsky, PE
通讯作者：
Lipsky, PE