SiO₂-induced release of sVEGFRs from pulmonary macrophages

The inhalation of silicon dioxide (SiO₂) particles causes silicosis, a stubborn pulmonary disease that is characterized by alveolar inflammation during the early stage. Soluble cytokine receptors (SCRs) play important roles in regulating inflammation by either attenuating or promoting cytokine signaling. However, the role of SCRs in silicosis remains unknown.

Luminex assays revealed increased soluble vascular endothelial growth factor receptor (sVEGFR) family levels in the plasma of silicosis patients. In an enzyme-linked immunosorbent assay (ELISA), cells from the differentiated human monocytic cell line U937 released sVEGFR family proteins after exposure to SiO₂ (50μg/cm²). Further Western blot experiments revealed that VEGFR expression was also elevated in U937 cells. In contrast, levels of sVEGFR family members did not change in the supernatants of human umbilical vein endothelial cells (HUVECs) after exposure to SiO₂ (50μg/cm²). Interestingly, VEGFR expression in HUVECs decreased after SiO₂ treatment. In a scratch assay, HUVECs exhibited cell migration ability, indicating the acquisition of mesenchymal properties.

Our findings highlight the important role of sVEGFRs in both inflammation and fibrosis induced by SiO₂, suggesting a possible mechanism for the fibrogenic effects observed in pulmonary diseases associated with fibrosis.