Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
J Neuroimmunol. 2011 Dec 15;240-241:58-64. doi: 10.1016/j.jneuroim.2011.09.012. Epub 2011 Oct 28.
Carbenoxolone (CBX) is a widely used gap-junction inhibitor. We have previously shown that treatment with CBX significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). However, the mechanism by which CBX delays the onset of EAE remains to be elucidated. Here, we show that CBX specifically inhibits the production of IL-23 by dendritic cells (DCs) and microglia in vitro. CBX treatment significantly reduced the population of Th17 cells in EAE mice. Furthermore, CBX downregulated the expression of IL-23 p19 via increased production of protein phosphatase 2A (PP2A). Thus, CBX may be an effective therapeutic strategy against Th17-mediated autoimmune diseases, such as multiple sclerosis.
卡波氯铵（CBX）是一种广泛应用的缝隙连接抑制剂。我们先前的研究表明，CBX 治疗可显著延迟实验性自身免疫性脑脊髓炎（EAE）的发病。然而，CBX 延迟 EAE 发病的机制仍有待阐明。本研究显示，CBX 可特异性抑制树突状细胞（DC）和小胶质细胞体外产生白细胞介素-23（IL-23）。CBX 处理可显著减少 EAE 小鼠中 Th17 细胞的数量。此外，CBX 通过增加蛋白磷酸酶 2A（PP2A）的产生而下调 IL-23 p19 的表达。因此，CBX 可能是一种针对 Th17 介导的自身免疫性疾病（如多发性硬化症）的有效治疗策略。
