Department of Immunology, Institute of Laboratory Medicine, Jiangsu University, Zhenjiang, China.
Scand J Immunol. 2012 Nov;76(5):483-90. doi: 10.1111/j.1365-3083.2012.02759.x.
High-mobility group box 1 (HMGB1) is a non-histone nuclear protein that is released extracellulary and has been implicated in autoimmune disease. Toll-like receptor 2 (TLR2) signalling is thought to be essential for the inflammatory response and for immune disorders. In recent studies, enhanced HMGB1 and TLR2 expressions have been found in rheumatoid arthritis (RA), respectively. The aim of this study is to explore whether HMGB1 stimulation can up-regulate the expression of TLR2 on CD14(+) monocytes from patients with RA and to clarify the subsequent events involving Th17 cells and Th17 cell-associated cytokine changes. Our results showed that the frequency of CD14(+) cells in peripheral blood mononuclear cell (PBMC) was obviously increased, and enhanced expression of TLR2 on CD14(+) monocytes was also found in patients with RA, compared with healthy controls with statistical significance (P < 0.001). In addition, the levels of IL-17, IL-23 and IL-6 in supernatants from cultured monocytes from patients and in patient's plasma were increased, and NF-κB, the downstream target of TLR2, also showed a marked elevation after monocytes were stimulated by HMGB1. This implies that the enhanced TLR2 pathway and Th17 cell polarization may be due to HMGB1 stimulation in rheumatoid arthritis.
高迁移率族蛋白 B1（HMGB1）是一种非组蛋白核蛋白，可释放到细胞外，并且与自身免疫性疾病有关。 Toll 样受体 2（TLR2）信号被认为对于炎症反应和免疫紊乱是必不可少的。在最近的研究中，类风湿关节炎（RA）患者中分别发现增强的 HMGB1 和 TLR2 表达。本研究旨在探讨 HMGB1 刺激是否可以上调 RA 患者 CD14（+）单核细胞中 TLR2 的表达，并阐明涉及 Th17 细胞和 Th17 细胞相关细胞因子变化的后续事件。我们的结果表明，与健康对照组相比，RA 患者外周血单个核细胞（PBMC）中 CD14（+）细胞的频率明显增加，并且 CD14（+）单核细胞中 TLR2 的表达也增强，具有统计学意义（P <0.001）。此外，培养的单核细胞上清液和患者血浆中 IL-17、IL-23 和 IL-6 的水平增加，并且 TLR2 的下游靶标 NF-κB 在单核细胞被 HMGB1 刺激后也明显升高。这意味着增强的 TLR2 途径和 Th17 细胞极化可能是由于类风湿关节炎中的 HMGB1 刺激。
