Characterization of interleukin-7 and interleukin-7 receptor in the pathogenesis of rheumatoid arthritis.
Characterization of interleukin-7 and interleukin-7 receptor in the pathogenesis of rheumatoid arthritis.
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DOI：
10.1002/art.30493
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发表时间：
2011-10
影响因子：
--
通讯作者：
Shahrara, Shiva
中科院分区：
文献类型：
--
作者：
Pickens, Sarah R.;Chamberlain, Nathan D.;Volin, Michael V.;Pope, Richard M.;Talarico, Nicholas E.;Mandelin, Arthur M., II;Shahrara, Shiva
本研究的目的是描述IL-7和IL-7 R在类风湿关节炎（RA）滑膜组织中的表达，并检查它们在巨噬细胞、内皮细胞和RA滑膜组织成纤维细胞中的调节和致病作用。免疫组化法检测RA及正常滑膜组织中IL-7及IL-7 R的表达。采用实时荧光定量RT-PCR和/或流式细胞术检测RA外周血中体外分化的巨噬细胞、RA滑膜组织成纤维细胞和人微血管内皮细胞（HMVECs）中IL-7和IL-7 R的表达和调节。接下来，使用ELISA检查IL-7活化的巨噬细胞、RA成纤维细胞和内皮细胞的促血管生成因子的产生。IL-7和IL-7 R共表达于RA滑膜组织衬里和亚衬里的巨噬细胞和内皮细胞。与正常细胞相比，RA滑膜液、外周血巨噬细胞和RA成纤维细胞中IL-7及其受体的表达明显升高。TLR 4连接和TNF-α刺激可调节RA巨噬细胞和HMVECs上IL-7和IL-7 R的表达。然而，在RA成纤维细胞中，LPS和TNF-α激活仅增加IL-7 R的表达。IL-7还通过诱导巨噬细胞和内皮细胞产生有效的促血管生成因子来介导RA发病机制。我们首次鉴定了RA成纤维细胞、RA外周血体外分化的巨噬细胞和内皮细胞中IL-7和IL-7 R表达的调节因子，并记录了IL-7在RA血管生成中的新作用。
The aim of the study was to characterize the expression of IL-7 and IL-7R in rheumatoid arthritis (RA) synovial tissue and to examine their regulation and pathogenic role in macrophages, endothelial cells and RA synovial tissue fibroblasts. Expression of IL-7 and IL-7R was demonstrated in RA and normal synovial tissues employing immunohistochemistry. Expression and regulation of IL-7 and IL-7R was determined in RA peripheral blood in vitro differentiated macrophages, RA synovial tissue fibroblasts and human microvascular endothelial cells (HMVECs) by real-time RT-PCR and/or flow cytometry. Next, IL-7 activated macrophages, RA fibroblasts and endothelial cells were examined for production of proangiogenic factors employing ELISA. IL-7 and IL-7R were coexpressed on RA synovial tissue lining and sublining macrophages and endothelial cells. Consistently, expression of IL-7 and its receptor were significantly elevated in RA synovial fluid and peripheral blood macrophages as well as RA fibroblasts compared to normal cells. TLR4 ligation and stimulation with TNF-α modulated expression of IL-7 and IL-7R on RA macrophages and HMVECs. However, in RA fibroblasts only expression of IL-7R was increased by LPS and TNF-α activation. IL-7 also mediated RA pathogenesis by inducing production of potent proangiogenic factors from macrophages and endothelial cells. We identify, for the first time, regulators of IL-7 and IL-7R expression in RA fibroblasts, RA peripheral blood in vitro differentiated macrophages and endothelial cells and we document a novel role of IL-7 in RA angiogenesis.
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影响因子：
5.4
作者：
Kroncke, R;Loppnow, H;Gerdes, J
通讯作者：
Gerdes, J
DOI：
10.1073/pnas.86.15.5923
发表时间：
1989-08-01
影响因子：
11.1
作者：
CHAZEN, GD;PEREIRA, GMB;SHEVACH, EM
通讯作者：
SHEVACH, EM
影响因子：
--
作者：
Shahrara, S;Proudfoot, AEI;Koch, AE
通讯作者：
Koch, AE
影响因子：
--
作者：
Hartgring, Sarita A. Y.;Willis, Cynthia R.;van Roon, Joel A. G.
通讯作者：
van Roon, Joel A. G.
影响因子：
15.3
作者：
Alderson, M R;Tough, T W;Ziegler, S F;Grabstein, K H
通讯作者：
Grabstein, K H