Huang QiQuan, Ma Yingyu, Adebayo Adedamola, Pope Richard M
Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Arthritis Rheum. 2007 Jul;56(7):2192-201. doi: 10.1002/art.22707.
Macrophages are the major source of inflammation mediators that are important in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to analyze macrophages obtained from the joints of RA patients in order to characterize the expression of Toll-like receptor 2 (TLR-2) and TLR-4 and the responses to TLR ligation.
Cells were isolated from the synovial fluid (SF) of RA patients or patients with other forms of inflammatory arthritis. Cell surface TLR-2 and TLR-4 expression and intracellular tumor necrosis factor alpha (TNFalpha) and interleukin-8 (IL-8) expression by CD14+ macrophages were determined by flow cytometry. Peptidoglycan (PG) and lipopolysaccharide (LPS) were used as ligands for TLR-2 and TLR-4, respectively.
The expression of TLR-2 and TLR-4 was increased on CD14+ macrophages from the joints of RA patients compared with that on control in vitro-differentiated macrophages or control peripheral blood monocytes. Neither TLR-2 expression nor TLR-4 expression differed between RA and other forms of inflammatory arthritis. However, PG- and LPS-induced TNFalpha expression and IL-8 expression were greater with RA SF macrophages than with those obtained from the joints of patients with other forms of inflammatory arthritis or with control macrophages. PG-induced TNFalpha expression and IL-8 expression were highly correlated with TLR-2 expression in normal macrophages, but not with that in macrophages obtained from joints of RA patients or patients with other forms of inflammatory arthritis.
TLR-2 and TLR-4 ligation resulted in increased activation of RA synovial macrophages compared with those from patients with other forms of inflammatory arthritis or compared with control macrophages. Factors other than the level of TLR-2 and TLR-4 expression contributed to the increased activation of RA SF macrophages. These observations support the notion of a potential role for activation through TLR-2 and TLR-4 in the inflammation and joint destruction of RA.
巨噬细胞是炎症介质的主要来源，在类风湿关节炎（RA）的发病机制中起重要作用。本研究旨在分析从RA患者关节中获取的巨噬细胞，以表征Toll样受体2（TLR-2）和TLR-4的表达以及对TLR连接的反应。
从RA患者或其他形式炎性关节炎患者的滑液（SF）中分离细胞。通过流式细胞术测定CD14+巨噬细胞的细胞表面TLR-2和TLR-4表达以及细胞内肿瘤坏死因子α（TNFα）和白细胞介素-8（IL-8）表达。肽聚糖（PG）和脂多糖（LPS）分别用作TLR-2和TLR-4的配体。
与体外分化的对照巨噬细胞或对照外周血单核细胞相比，RA患者关节中CD14+巨噬细胞上TLR-2和TLR-4的表达增加。RA与其他形式的炎性关节炎之间，TLR-2表达和TLR-4表达均无差异。然而，PG和LPS诱导的TNFα表达和IL-8表达在RA SF巨噬细胞中比在其他形式炎性关节炎患者关节中获取的巨噬细胞或对照巨噬细胞中更高。PG诱导的TNFα表达和IL-8表达在正常巨噬细胞中与TLR-2表达高度相关，但在从RA患者或其他形式炎性关节炎患者关节中获取的巨噬细胞中则不然。
与其他形式炎性关节炎患者的巨噬细胞或对照巨噬细胞相比，TLR-2和TLR-4连接导致RA滑膜巨噬细胞的激活增加。TLR-2和TLR-4表达水平以外的因素导致RA SF巨噬细胞的激活增加。这些观察结果支持通过TLR-2和TLR-4激活在RA的炎症和关节破坏中具有潜在作用的观点。
