HSP60 mediates the neuroprotective effects of curcumin by suppressing microglial activation
HSP60 mediates the neuroprotective effects of curcumin by suppressing microglial activation
复制标题
HSP60 通过抑制小胶质细胞激活介导姜黄素的神经保护作用
DOI：
10.3892/etm.2016.3413
复制
发表时间：
2016-08-01
影响因子：
2.7
通讯作者：
Wang, Yin
中科院分区：
文献类型：
--
作者：
Ding, Feijia;Li, Fan;Wang, Yin
姜黄素具有抗炎和抗氧化特性，已广泛用于治疗或预防神经退行性疾病。然而，姜黄素神经保护作用的机制尚不清楚。在本研究中，使用培养基的酶联免疫吸附测定和细胞裂解物的蛋白质印迹法研究了姜黄素对脂多糖（LPS）刺激的BV2小鼠小胶质细胞的影响。结果表明，姜黄素显着抑制LPS诱导的BV2细胞中热休克蛋白60（HSP60）的表达和释放。 LPS 激活的 BV2 小胶质细胞中热休克因子 (HSF)-1 的水平上调，表明 HSP60 表达的增加是由 HSF-1 激活驱动的。然而，姜黄素下调了增加的 HSF-1 水平。细胞外 HSP60 是 Toll 样受体 4 (TLR-4) 的配体，后者的水平在 LPS 激活的 BV2 小胶质细胞中增加，并被姜黄素抑制。已知 TLR-4 的激活与骨髓分化初级反应 88 (MyD88) 和核因子 (NF)-κ B 的激活相关，随后产生促炎因子和神经毒性因子。在本研究中，姜黄素可显着抑制 LPS 诱导的小胶质细胞中 MyD88、NF-kappa 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 beta 和 IL-6 的表达。这些结果表明姜黄素可能通过 HSP60/TLR-4/MyD88/NF-kappa B 信号通路抑制小胶质细胞活化来发挥其神经保护和抗炎作用。因此，姜黄素可能可用于治疗与小胶质细胞激活相关的神经退行性疾病。
Curcumin has anti-inflammatory and antioxidant properties and has been widely used to treat or prevent neurodegenerative diseases. However, the mechanisms underlying the neuroprotective effects of curcumin are not well known. In the present study, the effect of curcumin on lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells was investigated using enzyme-linked immunosorbent assays of the culture medium and western blotting of cell lysates. The results showed that curcumin significantly inhibited the LPS-induced expression and release of heat shock protein 60 (HSP60) in the BV2 cells. The level of heat shock factor (HSF)-1 was upregulated in LPS-activated BV2 microglia, indicating that the increased expression of HSP60 was driven by HSF-1 activation. However, the increased HSF-1 level was downregulated by curcumin. Extracellular HSP60 is a ligand of Toll-like receptor 4 (TLR-4), and the level of the latter was increased in the LPS-activated BV2 microglia and inhibited by curcumin. The activation of TLR-4 is known to be associated with the activation of myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-kappa B, with the subsequent production of proinflammatory and neurotoxic factors. In the present study, curcumin demonstrated marked suppression of the LPS-induced expression of MyD88, NF-kappa B, caspase-3, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin (IL)-1 beta and IL-6 in the microglia. These results indicate that curcumin may exert its neuroprotective and anti-inflammatory effects by inhibiting microglial activation through the HSP60/TLR-4/MyD88/NF-kappa B signaling wpathway. Therefore, curcumin may be useful for the treatment of neurodegenerative diseases that are associated with microglial activation.