Yoon Hee Jung, Jeon Sae Bom, Suk Kyoungho, Choi Dong-Kug, Hong Young-Joon, Park Eun Jung
Immune and Cell therapy Branch, National Cancer Center, Koyang 410-769, Korea.
Mol Cells. 2008 Feb 29;25(1):99-104.
Gangliosides, sialic acid-containing glycosphingolipids, are implicated in many neuronal diseases, but the precise molecular mechanisms underlying their pathological activities are poorly understood. Here we report that TLR2 participates in the initiation of ganglioside-triggered inflammatory signaling responses. Using FACS analysis and immunofluorescence microscopy, we found that gangliosides rapidly enhanced the cell surface expression of TLR2 in microglia, while reducing that of TLR4. The ganglioside-dependent increase of TLR2 expression was also observed at the messenger and protein levels. We also showed that gangliosides stimulate the interaction of TLR2 with Myd88, an adaptor for TLRs, and obtained evidence that lipid raft formation is closely associated with the ganglioside-induced activation of TLR2 and subsequent inflammatory signaling. These results collectively suggest that TLR2 contributes to the ability of gangliosides to cause inflammatory conditions in the brain.
神经节苷脂是含唾液酸的糖鞘脂，与许多神经疾病有关，但其病理活性背后的确切分子机制却知之甚少。在此我们报告，Toll样受体2（TLR2）参与神经节苷脂引发的炎症信号反应的起始过程。通过荧光激活细胞分选（FACS）分析和免疫荧光显微镜观察，我们发现神经节苷脂能迅速增强小胶质细胞表面TLR2的表达，同时降低TLR4的表达。在信使RNA和蛋白质水平也观察到神经节苷脂依赖的TLR2表达增加。我们还表明，神经节苷脂刺激TLR2与髓样分化因子88（Myd88，TLRs的衔接蛋白）的相互作用，并获得证据表明脂筏形成与神经节苷脂诱导的TLR2激活及随后的炎症信号密切相关。这些结果共同表明，TLR2促成了神经节苷脂在脑中引发炎症状态的能力。
