{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:51:59Z","timestamp":1760151119097,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["NIH\/NIEHS R01 ES027078"],"award-info":[{"award-number":["NIH\/NIEHS R01 ES027078"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["NIH\/NIA R21 AG067923-01"],"award-info":[{"award-number":["NIH\/NIA R21 AG067923-01"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Lead (Pb) is an environmental element that has been implicated in the development of dementia and Alzheimer\u2019s 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-\u03baB and p38 MAP kinase. Interestingly, both SB 203580, a p38 inhibitor, and BAY 11-7082, an NF-\u03baB p65 inhibitor, significantly blocked Pb-induced MCP-1 expression. However, SB203580 did not directly inhibit NF-\u03baB p65 phosphorylation. In conclusion, Pb exposure stimulates MCP-1 expression via the p38 and NF-\u03baB p65 pathways along with macrophage infiltration into the CP.<\/jats:p>","DOI":"10.3390\/biology11020308","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T22:43:22Z","timestamp":1644965002000},"page":"308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pb Induces MCP-1 in the Choroid Plexus"],"prefix":"10.3390","volume":"11","author":[{"given":"Huiying","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yundan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"School of Basic Medical Science, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s National Hospital, Washington, DC 20010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yansheng","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0041-008X(03)00251-5","article-title":"Brain barrier systems: A new frontier in metal neurotoxicological research","volume":"192","author":"Zheng","year":"2003","journal-title":"Toxicol. 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