IRF4 Participates in Pulmonary Fibrosis Induced by Silica Particles through Regulating Macrophage Polarization and Fibroblast Activation

In this study, RNA-seq analysis identified the upregulated expression ofIRF4 in fibrotic lung tissues of mice exposed to silica particles. And we verified the increased expression ofIRF4 in SiO2-treated macrophages and TGF- β1-treated fibroblasts. We further found that the down-regulation ofIRF4 impeded the macrophage polarization and the release of pro-fibrotic factors. Moreover, the down-regulation ofIRF4 alleviated the migration, invasion, and the expression of fibrotic molecules in fibroblasts. Using ChIP-qPCR assay, we confirmed thatIRF4 regulated the transcriptional activity of theIL-17A promoter, thus stimulated fibroblast activation, migration and invasion.In vivo experiment, the AAV-siIRF4 was designed to interfere with the expression ofIRF4 in lung tissues of mice exposed to silica particles. Whole blood, bronchoalveolar lavage fluid and lung tissues were obtained from mice at 7, 14, 28 and 56 days after silica exposure. The results showed that the leukocyte content and inflammatory factors reached a peak at day 14 and remained peak for a long time afterIRF4 knockdown. Furthermore, the fibrotic responses of mouse lung tissues were alleviated afterIRF4 knockdown.  Our study explored the important roles ofIRF4 in inflammatory and fibrotic responses, which provided a new target for the treatment of silicosis and pulmonary fibrosis.
Source: Inflammation - Category: Allergy & Immunology Source Type: research