Zhao Hua, Cheng Lei, Liu Yi, Zhang Wen, Maharjan Sailendra, Cui Zhaoqiang, Wang Xingli, Tang Dongqi, Nie Lin
J Mol Neurosci. 2014 Feb;52(2):186-92. doi: 10.1007/s12031-013-0120-7.
Microglia are important resident immune cells in the central nervous system (CNS) and involved in the neuroinflammation caused by CNS disorders, including brain trauma, ischemia, stroke, infections, inflammation, and neurodegenerative diseases. Our study explores the hypothesis that conserved dopamine neurotrophic factor (CDNF), a secretory neurotrophic factor, may provide a novel therapy for associated with neuroinflammation related to the microglia. We observed that CDNF was upregulated in rat primary microglia treated with 1 μg/mL lipopolysaccharide, an inflammatory inducer, for 24 h. Thus, we hypothesize that CDNF may play a role, mediator or inhibitor, in regulating the inflammation in microglial cells induced by LPS. Finally, our data showed that CDNF significantly attenuated the production of proinflammatory cytokines (PGE2 and IL-1β) and remarkably alleviated the cytotoxicity (percentage of lactate dehydrogenase released) in the LPS-induced microglia by suppressing the phosphorylation of JNK, but not the P38 or ERK pathways. These results demonstrate the anti-inflammatory property of CDNF by inhibition of JNK signaling in LPS-induced microglia, suggesting that CDNF may be a potential novel agent for the treatment of neuroinflammation in the CNS disorders.
小胶质细胞是中枢神经系统（CNS）中重要的常驻免疫细胞，参与由中枢神经系统疾病引起的神经炎症，包括脑外伤、缺血、中风、感染、炎症和神经退行性疾病。我们的研究探讨了一种假说，即保守多巴胺神经营养因子（CDNF），一种分泌性神经营养因子，可能为与小胶质细胞相关的神经炎症提供一种新的治疗方法。我们观察到，在用1μg/mL脂多糖（一种炎症诱导剂）处理24小时的大鼠原代小胶质细胞中，CDNF上调。因此，我们假设CDNF可能在调节由脂多糖诱导的小胶质细胞炎症中起作用，作为介质或抑制剂。最后，我们的数据表明，CDNF通过抑制JNK的磷酸化，而不是P38或ERK途径，显著减弱了促炎细胞因子（PGE2和IL-1β）的产生，并显著减轻了脂多糖诱导的小胶质细胞中的细胞毒性（乳酸脱氢酶释放百分比）。这些结果通过抑制脂多糖诱导的小胶质细胞中的JNK信号传导证明了CDNF的抗炎特性，表明CDNF可能是治疗中枢神经系统疾病中神经炎症的一种潜在新型药物。
