SiO₂ stimulates macrophage stress to induce the transformation of lung fibroblasts into myofibroblasts and its relationship with the sphingomyelin metabolic pathway

Abstract

Silicosis is a serious occupational disease with the highest incidence in China. However, its pathogenesis has not been fully elucidated. Studies have shown that the sphingomyelin signaling pathway may play an important role in different fibrotic diseases but its role in silicosis‐mediated fibrosis is still unclear. In this study, the supernatant of human peripheral blood mononuclear cell line (THP‐1)‐derived macrophages exposed to silica (SiO2) was used to stimulate the transformation of human embryonic lung fibroblast cell line (HFL‐1) into myofibroblasts, and the intervention effect of recombinant human acid ceramidase (rAC) was observed. The results showed that SiO2 stimulated the production of reactive oxygen species and malondialdehyde in the supernatant of THP‐1‐derived macrophages and increased the secretion of TGF‐β1, TNF‐α, and IL‐8. In addition, we found that the expression levels of α‐SMA, FN, Col I, and Col III in HFL‐1 cells increased. Meanwhile, the activities of ASMase and ACase and the expression levels of Cer, Sph, and S1P were increased. Intervention by rAC can suppress these changes to different degrees. In conclusion, the present study shows that SiO2 dust poisoning may stimulate HFL‐1 cell differentiation into myofibroblasts by inducing oxidative stress in THP‐1‐derived macrophages, thereby promoting the secretion of a variety of inflammatory factors and activating the sphingolipid signaling pathway in HFL‐1 cells. Exogenous rAC can effectively interfere with the stimulation of HFL‐1 cells by silica in vitro.

SiO2 dust induces inflammation and pulmonary fibrosis in rat lungs through activation of ASMase/ceramide pathway

“…Li et al, 2022). SiO 2 dust stimulates oxidative stress in macrophages, which activates the sphingolipid pathway and induces the conversion of human fetal lung fibroblast-1 (HFL-1) cells to myofibroblasts (Liu et al, 2021). These results suggest that the ASMase/ceramide signaling pathway, and sphingolipid molecules, may play a role in silica dust-induced lung injury, inflammation, and fibrosis.…”

“…Inhibition of the ASMase/ceramide signaling pathway halted the progression of fibrosis in mouse embryonic lung fibroblasts and ameliorated silica dust‐induced lung fibrosis in rats (Jin et al, 2014), and inhibition of ASMase ameliorates the SiO 2 dust‐induced cellular inflammatory and the EMT process in human bronchial epithelial (HBE) cells (Y. Li et al, 2022). SiO 2 dust stimulates oxidative stress in macrophages, which activates the sphingolipid pathway and induces the conversion of human fetal lung fibroblast‐1 (HFL‐1) cells to myofibroblasts (Liu et al, 2021). These results suggest that the ASMase/ceramide signaling pathway, and sphingolipid molecules, may play a role in silica dust‐induced lung injury, inflammation, and fibrosis.…”