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Immunopharmacol Immunotoxicol. 2019 Apr;41(2):199-206. doi: 10.1080/08923973.2019.1569046. Epub 2019 Feb 6.

Silica nanoparticles as an enhancer in the IL-1β-induced inflammation cycle of A549 cells.

Wu J1,2, Han Y1,2, Zou X1,2, Zhu K1,2, Wang Z2, Ye X1,2, Liu Y1,2, Dong S1,2, Chen X1,2, Liu D2, Wen Z2, Wang Y2, Huang S2, Zhou Z2, Zeng C2, Huang C2, Zheng S2, Du X2, Huang X2, Zhang B1, Jing C2,3, Yang G1,3.

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a Department of Pathogen Biology, School of Medicine , Jinan University , Guangzhou , China.
b Department of Epidemiology, School of Medicine , Jinan University , Guangzhou , China.
c Guangzhou Key Laboratory of Environmental Exposure and Health in Guangzhou , Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University , Guangzhou , Guangdong , China.


Objective: The industrial production and combustion of coal can produce silica nanoparticles (nano-SiO2). It enters the human body mainly through the respiratory tract and exerts a toxic effect. However, whether nano-SiO2 can increase the IL-1β-induced inflammatory expression in A549 cells has not been tested. Therefore, the synergistic toxicity of nano-SiO2 and IL-1β to A549 was observed in our study. Materials and methods: We exposed A549 cells to nano-SiO2 (0, 100, 500, and 1000 μg/ml) for 12 and 24 h. The effect of nano-SiO2 on the viability of A549 cells was observed by the CCK-8 method. The A549 cells were exposed to nano-SiO2 (1 mg/mL) and cytokine IL-1β (10 ng/mL) for 4 h, and we detected the expression of IL-1β and IL-6 cytokines by real time quantitative polymerase chain (RT-qPCR) and enzyme linked immunosorbent assay (ELISA). The expression of β-Actin, I-κB, phospho-ERK1/2 (P-ERK1/2), total-ERK1/2 (T-ERK1/2), phospho-JNK (P-JNK), total-JNK (T-JNK), phospho-P38 (P-P38), and total-P38 (T-P38) in A549 cells was detected by the Western Blot method. Results: The nano-SiO2 treatment resulted in a time-dependent decrease in the viability of A549 cells. The synergistic effect of nano-SiO2 and IL-1β was observed on the new production of IL-1β and IL-6 in A549 cells. The Western blot results showed that nano-SiO2 can increase the expression of IL-1β and IL-6 by promoting the phosphorylation of ERK1/2 and elevating the phosphorylation of I-κB by IL-1β. IL-1β and IL-6 were induced by nano-SiO2, and the IL-1β treatment with 20 μM of I-κBα phosphorylation inhibitor (PD98059) and 20 μM of ERK1/2 inhibitor (BAY11-7082) for 1 h was significantly lower than that of the control group in A549 cells. Discussion and conclusion: These results indicated that nano-SiO2 had a toxic effect on A549 cells, and this effect could increase IL-1β on the A549 cell-induced inflammatory response. The results suggested that the release of IL-1β and IL-6 in A549 was enhanced by the synergistic IL-1β-induced phosphorylation of ERK1/2 and I-κB. This process is similar to a snowball, and it is possible that IL-1β is continuously produced and repeatedly superimposed in A549 cells to produce an inflammatory effect; then, a vicious circle occurs, and an inflammatory storm is accelerated.


A549; IL-1β; IL-6; Silica nanoparticles; signaling pathway

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