High salt-induced activation and expression of inflammatory cytokines in cultured astrocytes
High salt-induced activation and expression of inflammatory cytokines in cultured astrocytes
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高盐诱导培养星形胶质细胞炎症细胞因子的激活和表达
DOI：
10.1080/15384101.2017.1301330
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发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Lu, Zhengqi
中科院分区：
文献类型：
--
作者：
Deng, Zhezhi;Wang, Yuge;Lu, Zhengqi
脑内盐（氯化钠，NaCl）的积累与多种中枢神经系统（CNS）疾病有关。星形胶质细胞的活化是中枢神经系统病理生理过程的重要表现。然而，高盐环境对星形胶质细胞的直接影响尚不清楚。在本研究中，我们发现高盐处理可以诱导星形胶质细胞在体内和体外活化，表现为形态改变和胶质纤维酸性蛋白（GFAP）表达增加。上调肿瘤坏死因子-α (TNF-α)、白细胞介素-6 （IL-6）、白细胞介素-1β (IL-1β)和血管内皮生长因子（VEGF）的表达；而对转化生长因子-β (TGF-β)表达影响不明显。此外，HS处理诱导信号换能器和激活因子转录3 （STAT 3）磷酸化增加。特异性药理拮抗剂AG490对Janus kinase 2 （JAK 2）的抑制作用分别减弱了JAK2/STAT3通路的激活和GFAP及其他促炎因子的诱导作用。上述结果提示，上述多种炎症细胞因子和介质可能通过JAK2/STAT3信号通路与HS诱导的中枢神经系统发病有关。
ABSTRACT Salt (sodium chloride, NaCl) accumulation in the brain is associated with various diseases of central nervous system (CNS). Activation of astrocytes is an important manifestation of pathophysiological processes in the CNS. However, the direct impact of high salt (HS) environment on astrocytes is unclear. In the current study, we found that high salt treatment can induce activation of astrocytes both in vivo and in vitro, manifested as morphological alteration coupled with increased expression of glial fibrillary acidic protein (GFAP). Additionally, HS upregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF); however, its effects on transforming growth factor-β (TGF-β) expression were not evident. Furthermore, HS treatment induced increased phosphorylation of signal transducer and activator transcription 3 (STAT 3). Inhibition of Janus kinase 2 (JAK 2) by specific pharmacological antagonists, AG490, attenuated the activation of JAK2/STAT3 pathway and induction of GFAP and other pro-inflammatory factors, respectively. The results suggest that the aforementioned multiple inflammatory cytokines and mediators that may be linked to the HS induced pathogenesis of CNS via the JAK2/STAT3 signaling pathways.