Oxymatrine inhibits microglia activation via HSP60-TLR4 signaling
Oxymatrine inhibits microglia activation via HSP60-TLR4 signaling
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氧化苦参碱通过 HSP60-TLR4 信号传导抑制小胶质细胞活化
DOI：
10.3892/br.2016.776
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发表时间：
2016-11-01
影响因子：
2.3
通讯作者：
Wang, Yin
中科院分区：
文献类型：
--
作者：
Ding, Feijia;Li, Yunhong;Wang, Yin
氧化苦参碱（OMT）是从苦参中提取的一种生物碱，具有广泛的抗炎、抗肿瘤和免疫抑制作用。然而，潜在的分子机制仍然难以捉摸。热休克蛋白60 （HSP60）最近被证明在自身免疫反应中起重要作用。本研究旨在探讨OMT是否通过抑制小胶质细胞激活来发挥其抗炎作用，并探讨HSP60在这一过程中的作用。Western blot和ELISA分析显示，OMT可降低脂多糖激活的BV2细胞HSP60的表达和释放。热休克因子1 （HSP60转录因子）的表达也受到OMT的抑制。细胞外HSP60已被证明通过toll样受体(TLR)-4途径诱导小胶质细胞凋亡。流式细胞术分析表明，LPS处理诱导BV2细胞凋亡，OMT在抑制LPS诱导的TLR-4表达的同时抑制了BV2细胞的凋亡。此外，OMT还能抑制髓样分化因子（MYD） 88、核因子(NF)- κ B、caspase-3、诱导型一氧化氮合酶、肿瘤坏死因子- α、白细胞介素(IL)-1 β和IL-6的水平。综上所述，OMT可能通过HSP60/TLR-4/MYD88/NF-kappa B信号通路发挥神经保护作用，抑制小胶质细胞的激活。因此，OMT可能为治疗与小胶质细胞激活相关的神经退行性疾病提供了巨大的治疗潜力。
Oxymatrine (OMT) is an alkaloid extracted from Sophora flavescens, which has broad anti-inflammatory, antitumor and immunosuppressant actions. However, the underlying molecular mechanisms have remained elusive. Heat shock protein 60 (HSP60) has recently been shown to have an important role in autoimmune reactions. The present study aimed to investigate whether OMT exerts its antiinflammatory effects by inhibiting microglial activation and examined the role of HSP60 in this process. Western blot analysis and ELISA showed that OMT decreased the expression and release of HSP60 by LPS-activated BV2 cells. The expression of heat shock factor 1, the transcription factor of HSP60, was also suppressed by OMT. Extracellular HSP60 has been previously indicated to induce microglial apoptosis through the Toll-like receptor (TLR)-4 pathway. Flow cytometric analysis demonstrated that LPS treatment induced apoptosis of BV2 cells, which was inhibited by OMT in parallel with inhibition of LPS-induced expression of TLR-4. Furthermore, OMT was shown to suppress the levels of myeloid differentiation factor (MYD) 88, nuclear factor (NF)-kappa B, caspase-3, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin (IL)-1 beta and IL-6. In light of these results, it was concluded that OMT may exert its neuroprotective effects via HSP60/TLR-4/MYD88/NF-kappa B signaling pathways to inhibit microglial activation. OMT may therefore offer substantial therapeutic potential for treating neurodegenerative diseases associated with microglial activation.