FTO Aggravates the Infiltration of Inflammatory Cells and Pulmonary Fibrosis in Silicosis Though Inducing the Imbalance of Macrophages Polarization.

Silicosis is a lung disease that is very harmful. This makes the disease worse. This study looks at how the fat mass and obesity associated (FTO) gene affects macrophage M1/M2 polarisation and pulmonary fibrosis in silicosis. Macrophages were isolated from alveolar lavage fluid in silicosis and bronchiectasis (BE) patients. Gene expression was detected by reverse transcription-PCR (RT-PCR). Pulmonary fibrosis was assessed by CT_FLV/TLV% using 3D CT and Masson staining assay. Enzyme-linked immunosorbent assay was applied to assess inflammatory factor level. The macrophage M1/M2 polarization characteristics (iNOS, CD206) was quantified by Immunofluorescence and Flow cytometry assays. Silicosis patients alveolar lavage macrophages polarized towards M1 type, and the expression level of M1 polarization-related chemokines also increased. More importantly, FTO gene downregulation promotes macrophage polarization to M1 type and the secretion of pro-inflammatory factor TNF-α and IL-6. And FTO knockdown can strengthen the glycolysis of macrophages, especially anaerobic glycolysis, thus inducing macrophages M1 polarization. Moreover, downregulation of FTO ameliorates silicosis pulmonary fibrosis. And FTO upregulation is associated with the M2 polarization of macrophage and the deterioration of pulmonary fibrosis in silicosis patients. FTO downregulation facilitates the infiltration of inflammatory cells by promoting M1 polarization of macrophages in silicosis.