Galectin-1 secreted by bone marrow-derived mesenchymal stem cells mediates anti-inflammatory responses in acute airway disease
Galectin-1 secreted by bone marrow-derived mesenchymal stem cells mediates anti-inflammatory responses in acute airway disease
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骨髓间充质干细胞分泌的半乳糖凝集素-1介导急性气道疾病的抗炎反应
DOI：
10.1016/j.yexcr.2021.112788
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发表时间：
2021-08-31
影响因子：
3.7
通讯作者：
Bai, Chong
中科院分区：
文献类型：
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作者：
Ge, Xiahui;Shi, Kehua;Bai, Chong
过敏性气道疾病（AAD）的标志包括炎性细胞浸润到支气管肺泡间隙。骨髓间充质干细胞（BMSCs）在AAD中显示出抗炎特性。此外，半乳糖凝集素-I（Gal-1）是在炎症时显著上调的凝集素，并且还已知介导潜在的抗炎反应。我们推测BMSCs通过分泌Gal-1调节AAD发病过程中的炎症反应。从小鼠股骨和胫骨分离BMSC，并过继转移到卵白蛋白诱导的AAD小鼠模型中。使用shRNA进行BMSC中Gal-1的敲低。采用流式细胞术、ELISA和免疫组织化学方法检测小鼠的炎症反应，并采用Transwell系统建立肺上皮细胞（MLE-12）与BMSCs的体外共培养体系。BMSCs的管理显着上调Gal-1的表达后，炎症和减少炎症细胞的浸润和分泌的促炎细胞因子在体内。此外，我们发现，这一功能是通过减少MAPK p38信号通路的激活介导的。当MLE-12细胞与BMSC共培养时，使用体外脂多糖诱导的模型也发现了类似的观察结果。BMSC分泌Gal-1减轻了AAD中观察到的炎症反应，因此为对常规药物治疗不敏感的AAD患者提供了一种有希望的治疗替代方案。
The hallmarks of allergic airway disease (AAD) include infiltration of inflammatory cells into the bronchoalveolar space. Bone marrow derived mesenchymal stem cells (BMSCs) show anti-inflammatory properties in AAD. In addition, galectin-1 (Gal-1) is a lectin significantly upregulated upon inflammation and is also known to mediate potential anti-inflammatory responses. We hypothesized that BMSCs regulated inflammatory responses by secretion of Gal-1 during AAD pathogenesis. BMSCs were isolated from murine femurs and tibiae and adoptively transferred into an ovalbumin-induced AAD mouse model. Knockdown of Gal-1 in BMSCs was performed using shRNA. Flow cytometry, ELISAs, and immunohistology were performed to analyze inflammatory responses in mice, and a Transwell system was used to establish an in vitro co-culture system of lung epithelial cells (MLE-12) and BMSCs. Administration of BMSCs significantly upregulated Gal-1 expression upon inflammation and decreased infiltration of inflammatory cells and secretion of proinflammatory cytokines in vivo. In addition, we showed that this function was mediated by reduced activation of the MAPK p38 signaling pathway. Similar observations were found using an in vitro lipopolysaccharide-induced model when MLE-12 cells were cocultured with BMSCs. Gal-1 secretion by BMSCs alleviated inflammatory responses observed in AAD and hence provides a promising therapeutic alternative to AAD patients insensitive to conventional drug treatments.