iTRAQ-based secretome reveals that SiO2 induces the polarization of RAW264.7 macrophages by activation of the NOD-RIP2-NF-κB signaling pathway

Abstract

Silicosis is characterized by inflammation and pulmonary fibrosis due to long-term inhalation of crystalline silica (SiO₂). To clarify the role of macrophage polarization in the inflammatory response of silicosis, we used iTRAQ-coupled 2D LC-MS/MS to study the change in the secretome in RAW264.7 macrophages. We successfully screened 330 differentially expressed proteins, including 120 proteins with upregulated expression and 210 proteins with down-regulated expression (p < 0.05). Bioinformatics analysis showed that the differentially expressed proteins were mainly involved in biological processes, such as oxidative stress, mitochondrial damage, apoptosis and acute inflammatory response. In particular, the expression levels of mitochondrial apoptosis-related proteins, such as AKT1, BAX, HSPD1, TNF, CASP8 and DAP, were increased after SiO₂ exposure. Taken together, our study indicated that SiO₂ could induce macrophage polarization by activation of the NOD-RIP2-NF-κB signaling pathway in RAW264.7 macrophages. This may represent a potential mechanism in the development of silicosis.

Keywords: Macrophage polarization; Secretome; Silicosis; iTRAQ.