Arthritis is associated with T-cell-induced upregulation of Toll-like receptor 3 on synovial fibroblasts.
Arthritis is associated with T-cell-induced upregulation of Toll-like receptor 3 on synovial fibroblasts.
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关节炎与 T 细胞诱导的滑膜成纤维细胞上 Toll 样受体 3 的上调有关。
DOI：
10.1186/ar3384
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发表时间：
2011-06-27
影响因子：
4.9
通讯作者：
Lu S
中科院分区：
文献类型：
--
作者：
Zhu W;Meng L;Jiang C;He X;Hou W;Xu P;Du H;Holmdahl R;Lu S
Toll样受体可能在类风湿性关节炎(RA)的发病机制中发挥重要作用。本研究的目的是确定滑膜中的关键TLRs，并探讨它们在关节炎T细胞介导的成纤维细胞样滑膜细胞(FLSS)激活中的作用。采用大鼠尾部皮下注射普瑞斯坦的方法，建立了普瑞斯坦诱导的关节炎模型。实时定量聚合酶链式反应检测不同时间点PIA大鼠滑膜组织中TLR的表达。PIA大鼠关节内注射多肌苷：多胞苷(Poly(I：C))，对关节炎进行宏观和微观监测。免疫组织化学方法检测滑膜组织中TLR3的表达。用Pristane诱导的T细胞或Pristane诱导的T细胞条件培养液刺激大鼠Fls。TLR3通过特异性短发夹状RNA(ShRNA)或抗体实现对FLSS的干预。划痕实验检测细胞的迁移能力，实时定量聚合酶链式反应(Real-time PCR)检测基因表达。用不同的细胞因子和TLR配体刺激类风湿关节炎患者的FLSS，用实时定量聚合酶链式反应检测TLR3的表达。此外，在不同浓度的聚(I：C)刺激下，比较类风湿关节炎(RA)和骨关节炎(OA)患者外周血中FLR3的表达。PIA大鼠滑膜TLR3早期持续过度表达。TLR3在FLSS中表达，Poly(I：C)局部治疗协同作用加重了关节炎。与普里斯坦诱导的T细胞共培养的大鼠外周血细胞的迁移能力增强，TLR3、干扰素-β、IL-6和基质金属蛋白酶3的表达显著上调，而普里斯坦诱导的T细胞条件培养液也能诱导其迁移。细胞因子和MMPs的上调可被shRNA或TLR3抗体阻断。在细胞因子或TLR配体刺激的RA FLSS中，TLR3的表达显著上调。此外，RA-FLSS对Poly(I：C)的反应性高于OA-FLSS。TLR3在PIA大鼠滑膜中过表达，TLR3信号通路的激活可加重PIA大鼠的关节炎。TLR3在FLSS中的诱导是由T细胞来源的炎症刺激引起的，并可能进一步介导FLS在关节炎中的激活。我们的结论是，T细胞激活的Flss上调TLR3导致关节炎症。
Toll-like receptors (TLRs) are likely to play crucial roles in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to determine the key TLRs in synovium and explore their roles in the activation of fibroblast-like synoviocytes (FLSs) mediated by T cells in arthritis. Pristane-induced arthritis (PIA) was established by subcutaneous injection with pristane at the base of the rat's tail. TLR expression in synovium from PIA rats was detected at different time points by performing real-time PCR. Polyinosinic:polycytidylic acid (poly(I:C)) was intra-articularly administrated to PIA rats, and arthritis was monitored macroscopically and microscopically. Synovial TLR3 was detected by immunohistochemical staining. Rat FLSs were stimulated with pristane-primed T cells or pristane-primed, T-cell conditioned medium. The intervention of TLR3 in FLSs was achieved by specific short-hairpin RNA (shRNA) or an antibody. The migration ability of FLSs was measured by using the scratch test, and gene expression was detected by using real-time PCR. FLSs from RA patients were stimulated with various cytokines and TLR ligands, and TLR3 expression was detected by performing real-time PCR. In addition, with different concentrations of poly(I:C) stimulation, TLR3 expression of FLSs from RA patients and patients with osteoarthritis (OA) was compared. Synovium TLR3 displayed early and persistent overexpression in PIA rats. TLR3 was expressed in FLSs, and local treatment with poly(I:C) synergistically aggravated the arthritis. Rat FLSs co-cultured with pristane-primed T cells showed strengthened migration ability and significant upregulation of TLR3, IFN-β, IL-6 and matrix metalloproteinase 3 (MMP3) expression, which could also be induced by pristane-primed, T-cell conditioned medium. The upregulation of cytokines and MMPs was blocked by shRNA or TLR3 antibodies. In RA FLSs with cytokine or TLR ligand stimulation, TLR3 expression exhibited remarkable upregulation. Furthermore, RA FLSs showed higher reactivity than OA FLSs to poly(I:C). TLR3 in the synovium of PIA rats was overexpressed, and activation of the TLR3 signaling pathway could aggravate this arthritis. The induction of TLR3 in FLSs resulted from T cell-derived inflammatory stimulation and could further mediate FLS activation in arthritis. We conclude that TLR3 upregulation of FLSs activated by T cells results in articular inflammation.
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影响因子：
4.4
作者：
Hoffmann, Markus H.;Tuncel, Jonatan;Steiner, Guenter
通讯作者：
Steiner, Guenter
DOI：
10.1186/ar330
发表时间：
2001
期刊：
Arthritis research
影响因子：
--
作者：
Liu ZQ;Deng GM;Foster S;Tarkowski A
通讯作者：
Tarkowski A
影响因子：
4.4
作者：
Kim, Kyoung-Woon;Cho, Mi-La;Kim, Ho-Youn
通讯作者：
Kim, Ho-Youn
影响因子：
4.4
作者：
Kim, Kyoung-Woon;Cho, Mi-La;Kim, Ho-Youn
通讯作者：
Kim, Ho-Youn
类风湿关节炎中滑膜细胞。滑膜成纤维细胞。
影响因子：
4.9
作者：
Mueller-Ladner, Ulf;Ospelt, Caroline;Gay, Steffen;Distler, Oliver;Pap, Thomas
通讯作者：
Pap, Thomas