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首页> 外文期刊>Cytokine >Galectin-3 is a sensor-regulator of toll-like receptor pathways in synovial fibroblasts
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Galectin-3 is a sensor-regulator of toll-like receptor pathways in synovial fibroblasts

机译：Galectin-3是滑膜成纤维细胞中Toll样受体途径的传感器调节剂

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Galectin-3 is a β-galactoside-binding lectin that plays an important role in the modulation of immune responses. It has been shown to aggravate joint inflammation and destruction in experimental arthritis. We investigated the role of galectin-3 in TLR-induced cell activation in human synovial fibroblasts (SF) in order to better understand the mechanism(s) of the proinflammatory function of galectin-3 in arthritis.Galectin-3 expression in SF obtained from rheumatoid arthritis and osteoarthritis patients was inhibited by siRNA mediated gene-knockdown. Galectin-3 was also inhibited with modified citrus pectin (MCP), a polysaccharide galectin-3 ligand. Galectin-3 knockdown inhibited TLR-2, -3 and -4-induced IL-6 secretion, but not TLR-2, -3 and -4-mediated matrix metalloproteinase-3 or CC chemokine ligand-5 secretion. When the SF were stimulated with phorbol 12-myristate 13-acetate, a protein kinase C activator that bypasses the membranal receptors, galectin-3 knockdown no longer influenced IL-6 secretion. MCP reduced IL-6 levels in a dose-dependent manner.Our results indicate that galectin-3 is a positive sensor-regulator of TLR-induced IL-6 secretion in human synovial fibroblasts, thus adding new insights into the mechanisms by which galectin-3 augments synovial inflammation. These findings corroborate the potential role of glycan inhibitors of galectin-3 as a therapeutic approach for the treatment of inflammatory arthritis.
机译：Galectin-3是一种β-半乳糖苷结合凝集素，在调节免疫应答中起重要作用。已经显示出它会加剧实验性关节炎中的关节发炎和破坏。我们研究了Galectin-3在人滑膜成纤维细胞（SF）中TLR诱导的细胞活化中的作用，以便更好地了解galectin-3在关节炎中的促炎作用的机制。类风湿关节炎和骨关节炎患者被siRNA介导的基因敲低抑制。 Galectin-3也被修饰的柑橘果胶（MCP）（一种多糖Galectin-3配体）抑制。 Galectin-3抑制可抑制TLR-2，-3和-4-诱导的IL-6分泌，但不抑制TLR-2，-3和-4-介导的基质金属蛋白酶3或CC趋化因子配体5的分泌。当用佛波醇12-肉豆蔻酸酯13-乙酸酯（绕过膜受体的蛋白激酶C激活剂）刺激SF时，galectin-3敲低不再影响IL-6分泌。 MCP以剂量依赖的方式降低IL-6的水平。我们的结果表明，galectin-3是TLR诱导的人滑膜成纤维细胞中IL-6分泌的阳性传感器调节剂，因此为galectin- 3加剧滑膜炎症。这些发现证实了galectin-3的聚糖抑制剂作为治疗炎性关节炎的治疗方法的潜在作用。

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