Angiogenesis in rheumatoid arthritis is fostered directly by toll-like receptor 5 ligation and indirectly through interleukin-17 induction.
Angiogenesis in rheumatoid arthritis is fostered directly by toll-like receptor 5 ligation and indirectly through interleukin-17 induction.
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DOI：
10.1002/art.37992
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发表时间：
2013-08
影响因子：
--
通讯作者：
Shahrara, Shiva
中科院分区：
文献类型：
--
作者：
Kim, Seung-jae;Chen, Zhenlong;Chamberlain, Nathan D.;Volin, Michael V.;Swedler, William;Volkov, Suncica;Sweiss, Nadera;Shahrara, Shiva
在这项研究中，我们专注于研究TLR 5对类风湿性关节炎（RA）内皮细胞功能和胶原诱导的关节炎（CIA）血管化的影响。采用内皮细胞迁移和管形成来证明TLR 5连接在血管生成中的直接作用。用TLR 5激动剂鞭毛蛋白处理CIA小鼠以记录TLR 5连接在RA病理学中的作用。通过组织学和关节细胞因子水平检查CIA血管化，并通过ELISA和FACS分析定量脾TH-17细胞。在RA外周血单核细胞中验证了通过TLR 5连接的TH-17细胞的发育。类风湿关节炎滑液中表达的内源性配体与TLR 5的连接有助于内皮细胞浸润和管腔形成。此外，发作后用鞭毛蛋白治疗加重CIA关节炎症，而在对照小鼠中，疾病活动达到平台期。我们表明，TLR 5增强疾病的严重程度是由于TH-17细胞分化和CIA关节血管化。当在RA外周血单个核细胞中检查潜在机制时，我们发现髓样TLR 5的连接及其TH-17促进细胞因子的产生是TH-17细胞极化所必需的。此外，我们证明，阻断IL-17级联可以显着减少鞭毛蛋白条件培养基激活的内皮细胞迁移，表明TLR 5连接可以直接通过吸引内皮细胞或间接通过促进TH-17细胞发育介导RA血管生成。我们的数据表明，类风湿关节炎血管生成中的TLR 5的一个新的作用，因此TLR 5可能是一个有前途的新的目标，类风湿关节炎治疗。
In this study we focus on examining the impact of TLR5 on rheumatoid arthritis (RA) endothelial cell function and collagen induced arthritis (CIA) vascularization. Endothelial migration and tube formation were employed to demonstrate the direct role of TLR5 ligation in angiogenesis. CIA mice were treated with TLR5 agonist, flagellin to document the effect of TLR5 ligation in RA pathology. CIA vascularization was examined by histology and joint cytokine levels and spleen TH-17 cells were quantified by ELISA and FACS analysis. Development of TH-17 cells by TLR5 ligation was validated in RA peripheral blood mononuclear cells. Ligation of TLR5 to endogenous ligands expressed in RA synovial fluid contributes to endothelial infiltration and tube formation. Further, post onset treatment with flagellin, exacerbates CIA joint inflammation while in the control mice, disease activity reaches the plateau phase. We show that TLR5 enhanced disease severity is due to TH-17 cell differentiation and CIA joint vascularization. When the underlying mechanism was examined in RA peripheral blood mononuclear cells, we found that ligation of myeloid TLR5 and their production of TH-17 promoting cytokines was necessary for TH-17 cell polarization. Additionally we demonstrate that blockade of IL-17 cascade can markedly reduce endothelial migration activated by flagellin condition media suggesting that TLR5 ligation can mediate RA angiogenesis either directly through attracting endothelial cells or indirectly by fostering TH-17 cell development. Our data demonstrate a novel role for TLR5 in RA angiogenesis hence TLR5 may be a promising new target for RA treatment.
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影响因子：
--
作者：
Grote K;Schütt H;Schieffer B
通讯作者：
Schieffer B
影响因子：
27.4
作者：
Chamberlain ND;Kim SJ;Vila OM;Volin MV;Volkov S;Pope RM;Arami S;Mandelin AM 2nd;Shahrara S
通讯作者：
Shahrara S
影响因子：
--
作者：
Pickens, Sarah R.;Chamberlain, Nathan D.;Volin, Michael V.;Pope, Richard M.;Talarico, Nicholas E.;Mandelin, Arthur M., II;Shahrara, Shiva
通讯作者：
Shahrara, Shiva
影响因子：
15.9
作者：
Abdollahi-Roodsaz, Shahla;Joosten, Leo A. B.;Van den Berg, Wim B.
通讯作者：
Van den Berg, Wim B.
影响因子：
4.4
作者：
Kim, Kyoung-Woon;Cho, Mi-La;Kim, Ho-Youn
通讯作者：
Kim, Ho-Youn