骨髓间充质干细胞分泌的抗炎蛋白TSG-6通过抑制巨噬细胞中的NLRP3炎症小体信号传导，缓解了二氧化硅诱导的急性肺部炎症。
Anti-inflammatory protein TSG-6 secreted by BMSCs attenuates silica-induced acute pulmonary inflammation by inhibiting NLRP3 inflammasome signaling in macrophages.
发表日期：2023 Sep 12
作者：
Wenyao Su, Qiying Nong, Jie Wu, Ruihong Fan, Yuanting Liang, Anyi Hu, Zhongxiang Gao, Weihui Liang, Qifei Deng, Hailan Wang, Lihua Xia, Yongshun Huang, Yiru Qin, Na Zhao
来源：
Int J Biol Macromol
摘要：
硅肺是一种严重的职业性肺部疾病，由于吸入了二氧化硅颗粒而引起。不幸的是，目前对硅肺的治疗选择有限。最近的研究进展表明，骨髓间质干细胞（BMSCs）对硅肺具有治疗作用，但其疗效和作用机制仍然大部分未知。在本研究中，我们重点研究了二氧化硅诱导的肺损伤的早期阶段，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炎症小体通路，减轻了硅引起的急性肺部炎症。为了进一步了解相关机制，我们利用RNA测序分析了与二氧化硅刺激的骨髓源巨噬细胞（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分泌的一种潜在重要旁分泌因子，具有保护作用。此外，当TSG-6表达被抑制时，BMSCs的抗炎症和炎症小体途径抑制效果在体内和体外都减弱。此外，用外源重组小鼠TSG-6（rmTSG-6）进行治疗显示出与BMSCs在减轻硅引起的炎症方面类似的效果。总的来说，我们的研究结果表明，BMSCs通过分泌TSG-6来调节巨噬细胞中炎症小体的激活，从而在体内和体外都对硅引起的急性肺部炎症具有保护作用。版权所有 © 2023. 由 Elsevier B.V. 发布。
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.Copyright © 2023. Published by Elsevier B.V.