An Soo Yeon, Youn Gi Soo, Kim Hyejin, Choi Soo Young, Park Jinseu
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
BMB Rep. 2017 Jan;50(1):25-30. doi: 10.5483/bmbrep.2017.50.1.114.
In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the NF-κB signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/NF-κB in astrocytes. [BMB Reports 2017; 50(1): 25-30].
在中枢神经系统中，病毒感染可通过上调促炎介质来诱导炎症，这些促炎介质有助于免疫细胞增强向中枢神经区域的浸润。已知雷公藤红素具有多种调节功能，包括抗菌活性。在本研究中，我们以多聚肌苷酸-多聚胞苷酸（poly(I:C)）（一种合成双链RNA）激活星形胶质细胞作为促炎介导反应的模型，研究了雷公藤红素的调节作用及其作用机制。雷公藤红素显著抑制了CRT-MG人星形胶质瘤细胞中poly(I:C)诱导的黏附分子（如ICAM-1/VCAM-1）和趋化因子（如CCL2、CXCL8和CXCL10）的表达。此外，雷公藤红素显著抑制了poly(I:C)诱导的JNK MAPK和STAT1信号通路的激活。此外，雷公藤红素显著抑制了poly(I:C)诱导的NF-κB信号通路的激活。这些结果表明，雷公藤红素可能通过抑制星形胶质细胞中JNK MAPK-STAT1/NF-κB的激活，从而抑制poly(I:C)诱导的促炎介质表达，发挥其调节活性。[《BMB报告》2017年；50(1): 25 - 30]
