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Issue 7, 2019
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Lanthanum chloride induces neuron damage by activating the nuclear factor-kappa B signaling pathway in activated microglia

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Abstract

Lanthanum is a rare earth element which can have adverse effects on the central nervous system (CNS). However, the mechanisms of these effects are not fully understood. The activated microglia plays an important role in the pathogenesis of neurodegenerative diseases and thus could be involved in mediating the toxic effects of lanthanum on the CNS. Nuclear factor-kappa B (NF-κB) is a critical nuclear factor which regulates the expression of inflammatory mediators in the activated microglia. This study investigated the effects of lanthanum chloride (LaCl3) on the NF-κB signaling pathway and explored the relationship between the microglia activation and neuron damage induced by La in vitro. The results showed that BV2 microglial cells treated with 0, 0.05, 0.1 or 0.2 mM LaCl3 could up-regulate the expression of Iba1 protein, a marker of microglia activation, and of p-IKKαβ and p-IκBα in a dose-dependent manner. La could also increase the translocation of the NF-κB p65 subunit from the cytosol into the nucleus, and then elevate the production of NO, TNF-α, IL-1β, IL-6 and MCP-1 by BV2 microglial cells. In a neuron–microglia co-culture system, BV2 microglia treated with LaCl3 resulted in a significant increase of the rates of neuron apoptosis. Conversely, the pre-treatment with PDTC (an inhibitor of the NF-κB signaling pathway) could inhibit the release of inflammatory cytokines and reduce the number of apoptotic neurons caused by La. These findings suggested that the neuron injury induced by LaCl3 might be related to the abnormal activation of microglia, which could remarkably increase the expression and release of pro-inflammatory cytokines via activating the NF-κB signaling pathway.

Graphical abstract: Lanthanum chloride induces neuron damage by activating the nuclear factor-kappa B signaling pathway in activated microglia

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Article information


Submitted
05 May 2019
Accepted
23 May 2019
First published
24 May 2019

Metallomics, 2019,11, 1277-1287
Article type
Paper

Lanthanum chloride induces neuron damage by activating the nuclear factor-kappa B signaling pathway in activated microglia

L. Yan, J. Yang, M. Yu, Y. Lu, L. Huang, J. Wang, X. Lu, C. Jin, S. Wu and Y. Cai, Metallomics, 2019, 11, 1277
DOI: 10.1039/C9MT00108E

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