Guangdong Province Hospital for Occupational Diseases Prevention and Treatment, Guangzhou 510300, China; Shunde Women and Children's Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, Guangdong 528300, China; School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
Guangdong Province Hospital for Occupational Diseases Prevention and Treatment, Guangzhou 510300, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 3):126651. doi: 10.1016/j.ijbiomac.2023.126651. Epub 2023 Sep 12.
Silicosis is a severe occupational lung disease caused by inhalation of silica particles. Unfortunately, there are currently limited treatment options available for silicosis. Recent advances have indicated that bone marrow mesenchymal stem cells (BMSCs) have a therapeutic effect on silicosis, but their efficacy and underlying mechanisms remain largely unknown. In this study, we focused on the early phase of silica-induced lung injury to investigate the therapeutic effect of BMSCs. Our findings demonstrated that BMSCs attenuated silica-induced acute pulmonary inflammation by inhibiting NLRP3 inflammasome pathways in lung macrophages. To further understand the mechanisms involved, we utilized RNA sequencing to analyze the transcriptomes of BMSCs co-cultured with silica-stimulated bone marrow-derived macrophages (BMDMs). The results clued tumor necrosis factor-stimulated gene 6 (TSG-6) might be a potentially key paracrine secretion factor released from BMSCs, which exerts a protective effect. Furthermore, the anti-inflammatory and inflammasome pathway inhibition effects of BMSCs were attenuated when TSG-6 expression was silenced, both in vivo and in vitro. Additionally, treatment with exogenous recombinant mouse TSG-6 (rmTSG-6) demonstrated similar effects to BMSCs in attenuating silica-induced inflammation. Overall, our findings suggested that BMSCs can regulate the activation of inflammasome in macrophages by secreting TSG-6, thereby protecting against silica-induced acute pulmonary inflammation both in vivo and in vitro.
矽肺是一种由吸入矽尘颗粒引起的严重职业性肺部疾病。不幸的是，目前针对矽肺的治疗选择有限。最近的研究进展表明，骨髓间充质干细胞（BMSCs）对矽肺具有治疗作用，但它们的疗效和潜在机制在很大程度上仍不清楚。在本研究中，我们专注于矽肺诱导的肺损伤早期阶段，以研究 BMSCs 的治疗效果。我们的研究结果表明，BMSCs 通过抑制肺巨噬细胞中的 NLRP3 炎性小体途径，减轻矽肺引起的急性肺炎症。为了进一步了解涉及的机制，我们利用 RNA 测序分析了与矽刺激的骨髓来源巨噬细胞（BMDMs）共培养的 BMSCs 的转录组。结果表明，肿瘤坏死因子刺激基因 6（TSG-6）可能是 BMSCs 释放的一种潜在关键旁分泌因子，发挥保护作用。此外，在体内和体外，沉默 TSG-6 表达均减弱了 BMSCs 的抗炎和炎性小体途径抑制作用。此外，用外源性重组小鼠 TSG-6（rmTSG-6）治疗可减轻矽肺诱导的炎症，与 BMSCs 具有相似的效果。总的来说，我们的研究结果表明，BMSCs 可以通过分泌 TSG-6 来调节巨噬细胞中炎性小体的激活，从而在体内和体外均能保护矽肺引起的急性肺炎症。
