The protective effects of bone marrow-derived mesenchymal stem cell (BMSC) on LPS-induced acute lung injury via TLR3-mediated IFNs, MAPK and NF-κB signaling pathways
The protective effects of bone marrow-derived mesenchymal stem cell (BMSC) on LPS-induced acute lung injury via TLR3-mediated IFNs, MAPK and NF-κB signaling pathways
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DOI：
10.1016/j.biopha.2016.02.037
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发表时间：
2016-04-01
影响因子：
7.5
通讯作者：
Mi, Xiuju
中科院分区：
文献类型：
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作者：
Wang, Jingcai;Qin, Ying;Mi, Xiuju
本研究旨在探讨骨髓间充质干细胞（BMSC）移植对内毒素（LPS）诱导的大鼠急性肺损伤（ALI）的保护作用。取大鼠骨髓，体外培养、扩增骨髓间充质干细胞。采用脂多糖（LPS）诱导大鼠急性肺损伤模型。雄性大鼠随机分为对照组、ALI组和骨髓间充质干细胞移植组。分别于BMSC注射后12、24、48 h处死大鼠。本研究旨在探讨BMSC在LPS诱导的肺泡巨噬细胞中的作用，以进一步阐明BMSC对肺损伤的作用机制。TLR 3是Toll样受体家族的成员之一，广泛存在于巨噬细胞和细胞表面。在我们的研究中，第一个BMSC成功地逆转LPS诱导的肺损伤的苏木精-伊红（H&E）染色，通过TUNEL和流式细胞仪分析改善细胞凋亡，以及改善细胞结构。Western blot、荧光定量PCR、免疫组化和免疫荧光分析证实BMSC处理后TLR 3表达显著下调。随后，TLR 3的下游信号TRIF和RIP 1被严重抑制，导致TRAF 3、MAPK以及NF-κ B B失活。结果表明，BMSC移植组通过TLR 3抑制LPS诱导的ALI中IFN水平，通过TLR 3调节的MAPK和NF-κ B信号通路抑制LPS诱导的肺损伤中的炎症反应。本研究表明，BMSC对LPS诱导的ALI具有保护作用，为临床治疗提供了实验依据。(C)2016 Elsevier Masson SAS。All rights reserved.
The study attempted to clarify the protective role of bone marrow-derived mesenchymal stem cell (BMSC) transplantation on LPS-induced acute lung injury (ALI) of rats. BMSC were obtained from bone marrow of rat, cultured and proliferated in vitro. Rats of ALI were established through lipopolysaccharide (LPS) administration. Male rats were allocated to control group, ALI group and BMSC, transplantation group. Rats were sacrificed after BMSC injection after 12 h, 24 h and 48 h. Here we investigated the role of BMSC in LPS-induced alveolar macrophages to further demonstrate the mechanism of BMSC to lung injury. TLR3, a member of Toll-like receptor family, has been found in macrophages and the cell surface. In our study, first BMSC successfully reversed LPS-induced lung injury by hematoxylin-eosin (H&E) staining, ameliorated apoptosis via TUNEL and flow cytometer analysis, as well as improved cell structure. And then, western blot, quantitative real-time PCR, immunohistochemistry and immunofluorescence analysis were used to confirm that TLR3 was significantly down-regulated for BMSC treatment. Subsequently, TRIF and RIP1, down-streaming signals of TLR3, were inhibited greatly, leading to TRAF3, MAPK as well as NF-kappa B inactivity. Our results indicated that BMSC transplantation group displayed inhibitory effects on interferon (IFNs) levels via TLR3 in LPS-induced ALI and preventive effects on inflammation response via TLR3-regualted MAPK and NF-kappa B signaling pathway in LPS-induced lung injury. The present study indicated that BMSC could display protective effects on LPS-induced ALI and provide an experimental basis for clinical therapy. (C) 2016 Elsevier Masson SAS. All rights reserved.