Pb Induces MCP-1 in the Choroid Plexus

Simple Summary: Our data in this study show that oral Pb exposure can induce MCP-1 expression along with monocyte and macrophage infiltration in the choroid plexus. Both NF-kappa B and p38 MAPK pathways modulate Pb-induced MCP-1 expression in CP epithelial cells.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-kappa B and p38 MAP kinase. Interestingly, both SB 203580, a p38 inhibitor, and BAY 11-7082, an NF-kappa B p65 inhibitor, significantly blocked Pb-induced MCP-1 expression. However, SB203580 did not directly inhibit NF-kappa B p65 phosphorylation. In conclusion, Pb exposure stimulates MCP-1 expression via the p38 and NF-kappa B p65 pathways along with macrophage infiltration into the CP.

Automated summary

The study demonstrates that oral exposure to lead can induce an increase in MCP-1 expression and infiltration of monocytes and macrophages in the choroid plexus. The activation of the p38 and NF-kappa B p65 pathways is involved in lead-induced MCP-1 expression.