Gu Huiying, Xu Yundan, Du Nicole, Yu Yongqi, Zheng Wei, Du Yansheng
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
School of Basic Medical Science, Hubei University of Chinese Medicine, Wuhan 430065, China.
Biology (Basel). 2022 Feb 15;11(2):308. doi: 10.3390/biology11020308.
Lead (Pb) is an environmental element that has been implicated in the development of dementia and Alzheimer's disease (AD). Additionally, innate immune activation contributes to AD pathophysiology. However, the mechanisms involved remain poorly understood. The choroid plexus (CP) is not only the site of cerebrospinal fluid (CSF) production, but also an important location for communication between the circulation and the CSF. In this study, we investigated the involvement of the CP during Pb exposure by evaluating the expression of the monocyte chemoattractant protein-1 (MCP-1). MCP-1 is highly expressed in the CP compared to other CNS tissues. MCP-1 regulates macrophage infiltration and is upregulated in AD brains. Our study revealed that Pb exposure stimulated MCP-1 expression, along with a significantly increased macrophage infiltration into the CP. By using cultured Z310 rat CP cells, Pb exposure stimulated MCP-1 expression in a dose-related fashion and markedly activated both NF-κB and p38 MAP kinase. Interestingly, both SB 203580, a p38 inhibitor, and BAY 11-7082, an NF-κB p65 inhibitor, significantly blocked Pb-induced MCP-1 expression. However, SB203580 did not directly inhibit NF-κB p65 phosphorylation. In conclusion, Pb exposure stimulates MCP-1 expression via the p38 and NF-κB p65 pathways along with macrophage infiltration into the CP.
铅（Pb）是一种环境元素，与痴呆症和阿尔茨海默病（AD）的发展有关。此外，先天免疫激活参与AD的病理生理过程。然而，其中涉及的机制仍知之甚少。脉络丛（CP）不仅是脑脊液（CSF）产生的部位，也是循环系统与脑脊液之间进行交流的重要场所。在本研究中，我们通过评估单核细胞趋化蛋白-1（MCP-1）的表达，研究了CP在铅暴露过程中的作用。与其他中枢神经系统组织相比，MCP-1在CP中高表达。MCP-1调节巨噬细胞浸润，且在AD脑内上调。我们的研究表明，铅暴露刺激MCP-1表达，同时巨噬细胞向CP的浸润显著增加。通过使用培养的Z310大鼠CP细胞，铅暴露以剂量相关的方式刺激MCP-1表达，并显著激活NF-κB和p38丝裂原活化蛋白激酶。有趣的是，p38抑制剂SB 203580和NF-κB p65抑制剂BAY 11-7082均显著阻断铅诱导的MCP-1表达。然而，SB203580并未直接抑制NF-κB p65的磷酸化。总之，铅暴露通过p38和NF-κB p65途径刺激MCP-1表达，并伴有巨噬细胞向CP的浸润。
