Effect of chemokine CC ligand 2 (CCL2) on α‑synuclein‑induced microglia proliferation and neuronal apoptosis

Zhang,Lijun; Ma,Pengju; Guan,Qingkai; Meng,Lei; Su,Linlin; Wang,Lina; Yuan,Bin

doi:10.3892/mmr.2018.9468

Effect of chemokine CC ligand 2 (CCL2) on α‑synuclein‑induced microglia proliferation and neuronal apoptosis

Authors:
- Lijun Zhang
- Pengju Ma
- Qingkai Guan
- Lei Meng
- Linlin Su
- Lina Wang
- Bin Yuan
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Affiliations: Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
Published online on: September 10, 2018 https://doi.org/10.3892/mmr.2018.9468
Pages: 4213-4218
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the effect of chemokine CC ligand 2 (CCL2) on α‑synuclein‑mediated microglia proliferation and neuronal apoptosis. Primary cultured microglia and primary neurons were isolated and cultured in vitro. Microglia were divided into four groups: The cells in the control group were treated with an identical amount of PBS, whereas the cells in the CCL2 group were cultured in medium containing 0.05 ng/µl CCL2; cells in the α‑synuclein group were treated with medium containing 0.2 ng/µl α‑synuclein; and cells in the CCL2 plus α‑synuclein group were cultured in medium containing 0.05 ng/µl CCL2 and 0.2 ng/µl α‑synuclein. After incubation for 24 h, the proliferation of glial cells, and the level of α‑synuclein in the cells, were measured. The levels of tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β) and nitric oxide (NO) in the culture medium were also measured. Levels of cleaved caspase‑3, Akt and phosphorylated (p)‑Akt in neurons treated with primary microglia culture medium in each group were subsequently monitored. The proliferation activity and secretion of TNF‑α, IL‑1β and NO in the CCL2, α‑synuclein and CCL2 plus α‑synuclein groups were significantly higher compared with that in the control group (P<0.05), as were the levels of α‑synuclein (P<0.01). The levels of neuronal apoptosis and cleaved caspase‑3 protein in the CCL2, α‑synuclein and CCL2 plus α‑synuclein groups were also significantly higher compared with that in the control group (P<0.01). Taken together, these results have demonstrated that CCL2 is able to promote α‑synuclein secretion and the apoptosis of neurons induced by α‑synuclein, thus inducing proliferation of the microglia and secretion of TNF‑α, IL‑1β and NO.

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