Gu Wen, Song Lin, Li Xiao-Ming, Wang Di, Guo Xue-Jun, Xu Wei-Guo
Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai 200092, China.
Sci Rep. 2015 Mar 4;5:8733. doi: 10.1038/srep08733.
Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD). Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism. We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages. In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks. Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages. In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK. Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways. This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism.
骨髓间充质干细胞（MSCs）已被确定为治疗慢性阻塞性肺疾病（COPD）的一种可能策略。我们之前的研究表明，间充质干细胞给药通过旁分泌机制在气道炎症和肺气肿方面具有治疗潜力。我们提出，间充质干细胞通过与巨噬细胞相互作用来逆转炎症过程并恢复受损的肺功能。在我们的研究中，大鼠暴露于香烟烟雾（CS）中，随后将间充质干细胞注入肺部，持续5周。在此我们表明，间充质干细胞给药通过下调环氧化酶-2（COX-2）以及COX-2介导的前列腺素E2（PGE2）生成来减轻气道炎症和肺气肿，这可能是通过对肺泡巨噬细胞的作用实现的。体外共培养实验提供了证据，表明间充质干细胞通过抑制与激活相关的p38丝裂原活化蛋白激酶（p38 MAPK）和细胞外信号调节激酶（ERK）磷酸化来下调巨噬细胞中的COX-2/PGE2。我们的数据表明，间充质干细胞可能通过抑制肺泡巨噬细胞中的COX-2/PGE2（部分由p38 MAPK和ERK途径介导）来缓解CS暴露大鼠模型中的气道炎症和肺气肿。这项研究为间充质干细胞治疗慢性阻塞性肺疾病提供了一个令人信服的机制，除了其旁分泌机制之外。
