Crucial role of pro-inflammatory cytokines from respiratory tract upon PM(2.5) exposure in causing the BMSCs differentiation in cells and animals.
Crucial role of pro-inflammatory cytokines from respiratory tract upon PM(2.5) exposure in causing the BMSCs differentiation in cells and animals.
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PM2.5 暴露后呼吸道促炎细胞因子在引起细胞和动物 BMSC 分化中的关键作用
DOI：
10.18632/oncotarget.23158
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发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Jin X;Su R;Li R;Cheng L;Li Z
细颗粒物暴露可能会导致健康风险，包括心血管疾病和癌症。骨髓间充质干细胞（BMSC）是评估污染物毒性的典型模型，由于其分化的特点，与这些疾病密切相关。因此，我们使用体外和体内模型研究了 PM2.5 暴露后 BMSC 的分化及其在呼吸道炎症激活中的作用。 PM2.5 处理的 16HBE 细胞的条件培养基响应增强了 BMSC 向内皮样细胞 (ELC) 和癌症相关成纤维细胞 (CAF) 的分化。 PM2.5升高16HBE细胞中炎症细胞因子的表达和分泌。然而，当向条件培养基中添加 IL-1β、IL-6 和 COX-2 中和抗体时，分化标记物的诱导会减弱。此外，PM2.5 诱导 16HBE 细胞中 ROS 形成和 NADPH 氧化酶 (NOX) 表达。 DPI（NOX ROS 抑制剂）或 NAC（ROS 抑制剂）补充剂可减少 PM2.5 诱导的炎症激活和 BMSC 分化。同样，观察到线粒体形态和呼吸链的伴随紊乱。此外，补充 Rot 或 AA（线粒体复合物 I 或 III 的抑制剂）可恢复 PM2.5 引起的毒性作用。此外，该结果与SD大鼠暴露于不同剂量PM2.5 30天后获得的体外数据一致。 PM2.5增强了SD大鼠呼吸器官（包括肺和气管组织）中BMSCs的分化和炎性细胞因子的表达。这项研究发现，PM2.5 通过呼吸道中 NOX 和线粒体诱导 ROS 介导的炎症激活来促进 BMSC 分化。
Fine particulate matter exposure may cause health risk, including cardiovascular diseases and cancer. Bone marrow mesenchymal stem cell (BMSC), a typical model for evaluating pollutant toxicity, has been closely linked to these diseases, due to its characteristics of differentiation. We therefore studied the BMSCs differentiation and its roles in inflammatory activation in the respiratory tract upon PM2.5 exposure using both in vitro and in vivo models. BMSCs differentiation into endothelial-like cells (ELCs) and cancer-associated fibroblasts cells (CAFs) was enhanced in response to conditioned medium from PM2.5–treated 16HBE cells. PM2.5 elevated inflammatory cytokines’ expression and secretion in 16HBE cells. However, induction of differentiation markers was reduced when IL-1β, IL-6 and COX-2 neutralizing antibodies were added to the conditioned medium. Furthermore, PM2.5 induced ROS formation and NADPH oxidase (NOX) expression in 16HBE cells. DPI (inhibitor of ROS from NOX) or NAC (inhibitor of ROS) supplement reduced PM2.5-induced inflammatory activation and BMSCs differentiation. Likewise, a concomitant disorder of mitochondrial morphology and respiratory chain was observed. In addition, Rot or AA (inhibitor of mitochondrial complex I or III) supplement restored PM2.5-induced toxic effects. Moreover, the results coincided with the in vitro data obtained from SD rats post-exposed to different doses of PM2.5 for 30 days. PM2.5 enhanced the BMSCs differentiation and inflammatory cytokines’ expression in respiratory organs of SD rats, including lung and trachea tissue. This study uncovers that PM2.5 promotes the BMSCs differentiation via inflammatory activation mediated by ROS induction from NOX and mitochondria in the respiratory tract.
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影响因子：
10.4
作者：
Haberzettl P;Lee J;Duggineni D;McCracken J;Bolanowski D;O'Toole TE;Bhatnagar A;Conklin DJ
通讯作者：
Conklin DJ
影响因子：
3.7
作者：
Carrion, Bita;Kong, Yen P.;Kaigler, Darnell;Putnam, Andrew J.
通讯作者：
Putnam, Andrew J.
影响因子：
3.7
作者：
Jin X;Song L;Liu X;Chen M;Li Z;Cheng L;Ren H
通讯作者：
Ren H
影响因子：
6.1
作者：
Corsini, Emanuela;Budello, Silvia;Galli, Corrado L.
通讯作者：
Galli, Corrado L.
太原市冬季典型时段环境PM2.5结合PAHs和NPAHs污染特征
影响因子：
9.1
作者：
Li, Rui-Jin;Kou, Xiao-Jing;Cai, Zong-Wei
通讯作者：
Cai, Zong-Wei