Section of Rheumatology and Immunology, Department of Internal Medicine, National Cheng Kung University Medical College, 1 Dashiue Road, Tainan, Taiwan.
Gene Ther. 2010 Oct;17(10):1225-33. doi: 10.1038/gt.2010.78. Epub 2010 Jun 3.
Different members of the galectin family may have inhibitory or stimulatory roles in controlling immune responses and regulating inflammatory reactions in autoimmune diseases such as rheumatoid arthritis (RA). A hypothetical model of a cross talk between galectin-1 and galectin-3 has been established in the circumstance of rheumatoid joints. As galectin-3 is a positive regulator and galectin-1 is a negative regulator of inflammation and autoimmune responses, in this study we evaluated the effects of local knockdown of galectin-3 or overexpression of galectin-1 on ameliorating collagen-induced arthritis (CIA) in rats. Lentiviral vectors encoding galectin-3 small hairpin RNA (shRNA) and galectin-1, as well as two control vectors expressing luciferase shRNA and green fluorescent protein, were individually injected intra-articularly into the ankle joints of rats with CIA, and their treatment responses were monitored by measuring the clinical, radiological and histological changes. Our results show that both knockdown of galectin-3 and overexpression of galectin-1 induced higher percentages of antigen-induced T-cell death in the lymph node cells from arthritic rats. Furthermore, these treatments significantly reduced articular index scores, radiographic scores and histological scores, accompanied with decreased T-cell infiltrates and reduced microvessel density in the ankle joints. Our findings implicate galectin-3 and galectin-1 as potential therapeutic targets for the treatment of RA.
不同的半乳糖凝集素家族成员可能在控制免疫反应和调节自身免疫性疾病（如类风湿关节炎）中的炎症反应方面具有抑制或刺激作用。在类风湿关节的情况下，已经建立了半乳糖凝集素-1 和半乳糖凝集素-3 之间相互作用的假设模型。由于半乳糖凝集素-3 是炎症和自身免疫反应的正调节剂，而半乳糖凝集素-1 是负调节剂，因此在这项研究中，我们评估了局部敲低半乳糖凝集素-3 或过表达半乳糖凝集素-1 对改善胶原诱导性关节炎（CIA）大鼠的影响。编码半乳糖凝集素-3 短发夹 RNA（shRNA）和半乳糖凝集素-1 的慢病毒载体，以及表达荧光素酶 shRNA 和绿色荧光蛋白的两个对照载体，分别被关节内注射到 CIA 大鼠的踝关节中，并通过测量临床、放射学和组织学变化来监测它们的治疗反应。我们的结果表明，敲低半乳糖凝集素-3 和过表达半乳糖凝集素-1 均诱导关节炎大鼠淋巴结细胞中抗原诱导的 T 细胞死亡百分比更高。此外，这些治疗方法显著降低了关节指数评分、放射评分和组织学评分，同时减少了踝关节中的 T 细胞浸润和微血管密度。我们的研究结果表明，半乳糖凝集素-3 和半乳糖凝集素-1 可能是治疗类风湿关节炎的潜在治疗靶点。
