Liu Ying, Zhan Feng, Zhang Xiao, Lin Shudian
Graduate School of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Rheumatology and Clinical Immunology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Exp Ther Med. 2018 Jan;15(1):585-591. doi: 10.3892/etm.2017.5411. Epub 2017 Oct 31.
The objective of the present study was to investigate the role of Toll-like receptor (TLR)-9 in B lymphocyte stimulating factor (BLyS)-induced systemic lupus erythematosus (SLE) in mice. The anti-double stranded (ds)DNA antibody titer, levels of complement proteins (C3 and C4), interleukin (IL)-10 and the disease activity [assessed by the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level] were measured. A total of 21 transgenic female mice (aged 8-10 weeks and weighing 30-40 g) expressing the Epstein-Barr virus membrane antigen, BLLF1, were studied. Mice were randomly divided into the control, the BLyS inhibition and the TLR-9 inhibition groups, with 7 mice in each group. Mice in the blank control group received intraperitoneal injections of normal saline, mice in the BLyS inhibition group received intraperitoneal injections of anti-BR3 monoclonal antibody (5,000 ng/day) and mice in the TLR-9 inhibition group received intraperitoneal injections of anti-human TLR-9 antibody (250 ng/day). The treatment regimens continued for 10 days, followed by the collection of peripheral venous blood. The relative levels of TLR-9 mRNA were measured by reverse transcription-quantitative polymerase chain reaction. Furthermore, the BLyS protein concentration and IL-10 levels were measured by ELISA. TLR-9 mRNA, BLyS, IL-10, anti-dsDNA antibody titer, C3, C4, ESR and CRP levels of the blank control group were significantly higher than those of the other two groups (P<0.05). The differences in comparison of these indexes between the BLyS inhibition and TLR-9 inhibition groups were not statistically significant (P>0.05), with the exception of TLR-9 mRNA and BLyS. In conclusion, the TLR-9 signaling pathway may be important for BLyS-induced SLE, and regulation of the inflammatory immune level.
本研究的目的是探讨Toll样受体（TLR）-9在B淋巴细胞刺激因子（BLyS）诱导的小鼠系统性红斑狼疮（SLE）中的作用。检测了抗双链（ds）DNA抗体滴度、补体蛋白（C3和C4）水平、白细胞介素（IL）-10以及疾病活动度[通过红细胞沉降率（ESR）和C反应蛋白（CRP）水平评估]。共研究了21只表达爱泼斯坦-巴尔病毒膜抗原BLLF1的转基因雌性小鼠（8至10周龄，体重30至40克）。小鼠被随机分为对照组、BLyS抑制组和TLR-9抑制组，每组7只。空白对照组小鼠腹腔注射生理盐水，BLyS抑制组小鼠腹腔注射抗BR3单克隆抗体（5000纳克/天），TLR-9抑制组小鼠腹腔注射抗人TLR-9抗体（250纳克/天）。治疗方案持续10天，随后采集外周静脉血。通过逆转录-定量聚合酶链反应测量TLR-9 mRNA的相对水平。此外，通过酶联免疫吸附测定法测量BLyS蛋白浓度和IL-10水平。空白对照组的TLR-9 mRNA、BLyS、IL-10、抗dsDNA抗体滴度、C3、C4、ESR和CRP水平显著高于其他两组（P<0.05）。除TLR-9 mRNA和BLyS外，BLyS抑制组和TLR-9抑制组之间这些指标比较的差异无统计学意义（P>0.05）。总之，TLR-9信号通路可能对BLyS诱导的SLE以及炎症免疫水平的调节很重要。
