PMID- 35205174 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240326 IS - 2079-7737 (Print) IS - 2079-7737 (Electronic) IS - 2079-7737 (Linking) VI - 11 IP - 2 DP - 2022 Feb 15 TI - Pb Induces MCP-1 in the Choroid Plexus. LID - 10.3390/biology11020308 [doi] LID - 308 AB - 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-kappaB and p38 MAP kinase. Interestingly, both SB 203580, a p38 inhibitor, and BAY 11-7082, an NF-kappaB p65 inhibitor, significantly blocked Pb-induced MCP-1 expression. However, SB203580 did not directly inhibit NF-kappaB p65 phosphorylation. In conclusion, Pb exposure stimulates MCP-1 expression via the p38 and NF-kappaB p65 pathways along with macrophage infiltration into the CP. FAU - Gu, Huiying AU - Gu H AD - Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. FAU - Xu, Yundan AU - Xu Y AD - Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. AD - School of Basic Medical Science, Hubei University of Chinese Medicine, Wuhan 430065, China. FAU - Du, Nicole AU - Du N AD - Department of Pediatrics, Children's National Hospital, Washington, DC 20010, USA. FAU - Yu, Yongqi AU - Yu Y AD - Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. FAU - Zheng, Wei AU - Zheng W AD - School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA. FAU - Du, Yansheng AU - Du Y AD - Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. LA - eng GR - R01 ES027078/ES/NIEHS NIH HHS/United States GR - NIH/NIA R21 AG067923-01/AG/NIA NIH HHS/United States GR - NIH/NIEHS R01 ES027078/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20220215 PL - Switzerland TA - Biology (Basel) JT - Biology JID - 101587988 PMC - PMC8869661 OTO - NOTNLM OT - Alzheimer's disease OT - MCP-1 OT - NF-kappaB OT - Z310 OT - choroid plexus OT - lead OT - macrophage infiltration OT - p38 MAP kinase COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2022/02/26 06:00 MHDA- 2022/02/26 06:01 PMCR- 2022/02/15 CRDT- 2022/02/25 01:06 PHST- 2022/01/03 00:00 [received] PHST- 2022/02/06 00:00 [revised] PHST- 2022/02/10 00:00 [accepted] PHST- 2022/02/25 01:06 [entrez] PHST- 2022/02/26 06:00 [pubmed] PHST- 2022/02/26 06:01 [medline] PHST- 2022/02/15 00:00 [pmc-release] AID - biology11020308 [pii] AID - biology-11-00308 [pii] AID - 10.3390/biology11020308 [doi] PST - epublish SO - Biology (Basel). 2022 Feb 15;11(2):308. doi: 10.3390/biology11020308.