Deng G M, Tarkowski A
Department of Rheumatology, University of Göteborg, Sweden.
Arthritis Rheum. 2000 Feb;43(2):356-64. doi: 10.1002/1529-0131(200002)43:2<356::AID-ANR15>3.0.CO;2-J.
To investigate the features of arthritis induced by bacterial DNA that contain CpG motifs.
Bacterial DNA originating from Escherichia coli and Staphylococcus aureus or synthetic oligonucleotides containing CpG motifs were injected directly into knee joints of mice. Histopathologic joint damage, antibody levels, cytokine levels, and synovial messenger RNA (mRNA) expression of cytokines and chemokines were assessed.
Histopathologic signs of arthritis were evident within 2 hours and lasted for at least 3 weeks. Nonmethylated CpG motifs were responsible for the induction of arthritis since oligonucleotides containing these motifs triggered arthritis, whereas methylation of these nucleotides abrogated the inflammatory response. Arthritis was characterized by an influx of monocytic, Mac-1+ cells and by a scarcity of T lymphocytes. The disease was characterized locally by mRNA expression of macrophage-derived cytokines (tumor necrosis factor alpha, interleukin-12 [IL-12], IL-1beta) and chemokines (monocyte chemoattractant protein 1, RANTES) in arthritic joints. Systemically, the arthritis was characterized by increased levels of circulating IL-6 and immunoglobulins.
These findings demonstrate that bacterial DNA that contain nonmethylated CpG motifs induces arthritis, suggesting an important pathogenic role for bacterial DNA in septic arthritis.
研究含CpG基序的细菌DNA诱导的关节炎特征。
将源自大肠杆菌和金黄色葡萄球菌的细菌DNA或含CpG基序的合成寡核苷酸直接注射到小鼠膝关节内。评估组织病理学关节损伤、抗体水平、细胞因子水平以及细胞因子和趋化因子的滑膜信使核糖核酸（mRNA）表达。
关节炎的组织病理学迹象在2小时内明显出现，并持续至少3周。未甲基化的CpG基序是诱导关节炎的原因，因为含有这些基序的寡核苷酸引发了关节炎，而这些核苷酸的甲基化消除了炎症反应。关节炎的特征是单核细胞、Mac-1+细胞流入，T淋巴细胞稀少。该疾病在局部表现为关节炎关节中巨噬细胞衍生的细胞因子（肿瘤坏死因子α、白细胞介素-12 [IL-12]、IL-1β）和趋化因子（单核细胞趋化蛋白1、调节激活正常T细胞表达和分泌因子）的mRNA表达。在全身，关节炎的特征是循环中IL-6水平和免疫球蛋白水平升高。
这些发现表明，含未甲基化CpG基序的细菌DNA可诱导关节炎，提示细菌DNA在脓毒性关节炎中具有重要的致病作用。
