Neuroinflammation triggered by activation of glial cells plays an important role in the pathophysiology of several neurodegenerative diseases including Parkinson's disease (PD). Besides microglia, astrocytes are also critical in initiating and perpetuating inflammatory process associated with PD. Heat shock protein 70 (Hsp70) is originally described as intracellular chaperone, however, recent study revealed that it had anti-inflammatory effects as well. The present study is designed to investigate whether Hsp70 mediates neuroinflammation in astrocytes. By employing α-synuclein (α-Syn) (A53T) aggregates on primary cultured astrocytes of rats, we found that astrocytes were activated and neuroinflammatory response was triggered, as indicated by over-expression of glial fibrillary acidic protein (GFAP), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), increased production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The data also showed that the neuroinflammatory response accompanied up-regulated Hsp70 expression. Moreover, over-expression of Hsp70 through transfection of Hsp70 cDNA plasmids could significantly reduce the production of TNF-α, IL-1β, and the expression of GFAP, COX-2 as well as iNOS. While inhibition of Hsp70 by VER155008 exacerbated neuroinflammatory response in astrocytes challenged by α-Syn aggregates. Further mechanistic study indicated that c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) signalings were responsible for the neuroinflammation, which was also regulated by Hsp70. These findings demonstrated that Hsp70 was an important modulator in astrocytes induced inflammation, and up-regulation of Hsp70 might be a potential regulating approach for neuroinflammation-related neurodegenerative diseases, such as PD.

由神经胶质细胞激活触发的神经炎症在包括帕金森氏病（PD）在内的几种神经退行性疾病的病理生理中起着重要作用。除了小胶质细胞外，星形胶质细胞在引发和延续与PD相关的炎症过程中也至关重要。热休克蛋白70（Hsp70）最初被描述为细胞内伴侣，但是最近的研究表明它也具有抗炎作用。本研究旨在调查Hsp70是否介导星形胶质细胞的神经炎症。通过在大鼠原代培养的星形胶质细胞上使用α-突触核蛋白（α-Syn）（A53T）聚集体，我们发现星形胶质细胞被激活并触发了神经炎症反应，如神经胶质纤维酸性蛋白（GFAP）的过表达所表明的，环氧合酶2（COX-2）和诱导型一氧化氮合酶（iNOS）可增加肿瘤坏死因子-α（TNF-α）和白介素1β（IL-1β）的产生。数据还表明，神经炎症反应伴随着Hsp70表达的上调。此外，通过转染Hsp70 cDNA质粒过表达Hsp70可以显着降低TNF-α，IL-1β的产生以及GFAP，COX-2和iNOS的表达。尽管VER155008对Hsp70的抑制作用加剧了α-Syn聚集体挑战的星形胶质细胞的神经炎症反应。进一步的机理研究表明，c-Jun N末端激酶（JNK）和核因子-κB（NF-κB）信号是神经炎症的原因，其也受到Hsp70的调节。这些发现表明，Hsp70是星形胶质细胞诱导炎症的重要调节剂，