Chronic inflammation and fibrosis are characteristics of silicosis, and the inflammatory mediators involved in silicosis have not been fully elucidated. Recently, macrophage-derived exosomes have been reported to be inflammatory modulators, but their role in silicosis has not been explored. The purpose of the present study was to investigate the role of macrophage-derived exosomal high mobility group box 3 (HMGB3) in silica-induced pulmonary inflammation. The induction of the inflammatory response and the recruitment of monocytes/macrophages were evaluated by immunofluorescence, flow cytometry and transwell assays. The expression of inflammatory cytokines was examined by RT–PCR and ELISA, and the signalling pathways involved were examined by western blot analysis. HMGB3 expression was increased in exosomes derived from silica-exposed macrophages. Exosomal HMGB3 significantly upregulated the expression of inflammatory cytokines, activated the STAT3/MAPK (ERK1/2 and p38)/NF-κB pathways in monocytes/macrophages, and promoted the migration of these cells by CCR2. Exosomal HMGB3 is a proinflammatory modulator of silica-induced inflammation that promotes the inflammatory response and recruitment of monocytes/macrophages by regulating the activation of the STAT3/MAPK/NF-κB/CCR2 pathways.

中文翻译：

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巨噬细胞衍生的外泌体 HMGB3 通过促进 M1 巨噬细胞极化和招募来调节二氧化硅诱导的肺部炎症

慢性炎症和纤维化是矽肺的特征，而参与矽肺的炎症介质尚未完全阐明。最近，据报道巨噬细胞来源的外泌体是炎症调节剂，但其在矽肺中的作用尚未被探索。本研究的目的是探讨巨噬细胞源性外泌体高迁移率族蛋白 3 (HMGB3) 在二氧化硅诱导的肺部炎症中的作用。通过免疫荧光、流式细胞术和跨孔测定评估炎症反应的诱导和单核细胞/巨噬细胞的募集。通过RT-PCR和ELISA检测炎症细胞因子的表达，并通过蛋白质印迹分析检测涉及的信号通路。暴露于二氧化硅的巨噬细胞衍生的外泌体中 HMGB3 表达增加。外泌体HMGB3显着上调炎症细胞因子的表达，激活单核细胞/巨噬细胞中的STAT3/MAPK（ERK1/2和p38）/NF-κB通路，并通过CCR2促进这些细胞的迁移。外泌体 HMGB3 是二氧化硅诱导炎症的促炎调节剂，通过调节 STAT3/MAPK/NF-κB/CCR2 通路的激活来促进炎症反应和单核细胞/巨噬细胞的募集。