Toll-like receptor 3 upregulation in macrophages participates in the initiation and maintenance of pristane-induced arthritis in rats.
Toll-like receptor 3 upregulation in macrophages participates in the initiation and maintenance of pristane-induced arthritis in rats.
复制标题
巨噬细胞中 Toll 样受体 3 的上调参与了降植烷诱导的大鼠关节炎的发生和维持。
DOI：
10.1186/ar3034
复制
发表时间：
2010
影响因子：
4.9
通讯作者：
Lu S
中科院分区：
文献类型：
--
作者：
Meng L;Zhu W;Jiang C;He X;Hou W;Zheng F;Holmdahl R;Lu S
Toll样受体（Toll like receptor，TLR）参与了先天性和适应性免疫应答，在类风湿性关节炎（RA）和实验性关节炎的发病机制中起着复杂的作用。本研究的目的是确定降植烷诱导的关节炎（PIA），RA大鼠模型中的关键TLR，并阐明其在关节炎的启动和维持中的作用。用降植烷诱导DA大鼠关节炎模型，通过肉眼和显微镜评分系统评价关节炎的严重程度。采用实时荧光定量聚合酶链反应（PCR）和流式细胞术检测不同时间点脾脏TLR和细胞因子的表达。在PIA大鼠体内分别应用聚肌苷-聚胞苷酸（polyI：C，TLR 3的配体）或TLR 3特异性短发夹RNA质粒进行RNA干扰。采用Griess法测定血清一氧化氮浓度，采用L929 biotest法测定肿瘤坏死因子α（TNF-α）。在脾巨噬细胞中，通过流式细胞术测量TLR 3表达。用降植烷刺激大鼠巨噬细胞系NR 8383，用抗TLR 3抗体阻断TLR 3通路。实时荧光定量PCR检测NR 8383细胞TLR 3和细胞因子的表达。通过筛选降植烷注射后DA大鼠脾脏中TLR的表达谱，我们发现TLR 3是最早且显著上调的TLR。在注射降植烷后第6天和第26天，脾脏TLR 3 mRNA和蛋白表达均上调。此外，给予polyI：C加剧了关节炎，而靶向TLR 3的RNA干扰改善了关节炎。特别地，TLR 3表达在PIA大鼠的脾巨噬细胞中被诱导，并且在降植烷刺激后也以剂量和时间依赖性方式在NR 8383细胞系中被诱导。通过降植烷刺激的干扰素β（IFN-β）和TNF-α的上调被NR 8383中的抗TLR 3抗体阻断。TLR 3在PIA的发生、发展中起关键作用，PIA可能依赖于巨噬细胞。这些发现有助于了解RA的发病机制，并可能为RA的治疗提供一个有趣的机会。
Toll-like receptors (TLRs) are involved in both innate and adaptive immune responses and are likely to play a complex role in the pathogenesis of human rheumatoid arthritis (RA) and experimental arthritis. The objective of this study was to identify the key TLR in pristane-induced arthritis (PIA), a rat model for RA, and to clarify its roles in the initiation and maintenance of arthritis. Arthritis in DA rats was induced by pristane and the severity was evaluated by macroscopic and microscopic score systems. Spleen TLR and cytokine expression was detected at different time points by real-time polymerase chain reaction (PCR) and flow cytometry. Polyinosine-polycytidylic acid (polyI:C, a ligand of TLR3) or TLR3 specific short-hairpin RNA plasmid for RNA interference was administrated to PIA rats in vivo. Serum nitrogen oxide concentration was determined by Griess method, and tumor necrosis factor alpha (TNF-α) was determined by L929 biotest. In splenic macrophages, TLR3 expression was measured by flow cytometry. A rat macrophage cell line (NR8383) was stimulated by pristane, and anti-TLR3 antibody were used to block TLR3 pathway. TLR3 and cytokine expression in NR8383 were detected by real-time PCR. By screening the TLR expression profile in spleen of DA rats after pristane injection, we found that TLR3 was the most early and prominently upregulated TLR. Both TLR3 mRNA and protein expression of spleen were upregulated at 6 and 26 days after pristane injection. Furthermore, administration of polyI:C exacerbated, whereas RNA interference targeting TLR3 ameliorated, the arthritis. Particularly, TLR3 expression was induced in splenic macrophages of PIA rats, and also in the NR8383 cell line after pristane stimulation in a dose- and time- dependent manner. Upregulation of interferon beta (IFN-β) and TNF-α by pristane stimulation was blocked by anti-TLR3 antibody in NR8383. TLR3 plays a pivotal role in the initiation and development of PIA which may dependent on macrophage. These findings are useful to understand the pathogenesis of RA and may provide an intriguing therapeutic opportunity for RA.
登录
查看更多内容
影响因子：
32.4
作者：
Herlands, Robin A.;Christensen, Sean R.;Sweet, Rebecca A.;Hershberg, Uri;Shlomchik, Mark J.
通讯作者：
Shlomchik, Mark J.
影响因子：
32.4
作者：
Isnardi I;Ng YS;Srdanovic I;Motaghedi R;Rudchenko S;von Bernuth H;Zhang SY;Puel A;Jouanguy E;Picard C;Garty BZ;Camcioglu Y;Doffinger R;Kumararatne D;Davies G;Gallin JI;Haraguchi S;Day NK;Casanova JL;Meffre E
通讯作者：
Meffre E
影响因子：
4.4
作者：
Hoffmann, Markus H.;Tuncel, Jonatan;Steiner, Guenter
通讯作者：
Steiner, Guenter
影响因子：
56.9
作者：
Asagiri, Masataka;Hirai, Toshitake;Takayanagi, Hiroshi
通讯作者：
Takayanagi, Hiroshi
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.