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

Abstract

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-ERK_1/2 (P-ERK_1/2), total-ERK_1/2 (T-ERK_1/2), 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 ERK_1/2 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 ERK_1/2 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 ERK_1/2 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.

Keywords: A549; IL-1β; IL-6; Silica nanoparticles; signaling pathway.