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

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.