Mesenchymal stromal cells alleviate acute respiratory distress syndrome through the cholinergic anti-inflammatory pathway.
Mesenchymal stromal cells alleviate acute respiratory distress syndrome through the cholinergic anti-inflammatory pathway.
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间充质基质细胞通过胆碱能抗炎途径缓解急性呼吸窘迫综合征
DOI：
10.1038/s41392-022-01124-6
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发表时间：
2022-09-05
影响因子：
39.3
通讯作者：
Xiang, Andy Peng
中科院分区：
文献类型：
--
作者：
Zhang, Xiaoran;Wei, Xuxia;Deng, Yiwen;Yuan, Xiaofeng;Shi, Jiahao;Huang, Weijun;Huang, Jing;Chen, Xiaoyong;Zheng, Shuwei;Chen, Jieying;Chen, Keyu;Xu, Ruiming;Wang, Hongmiao;Li, Weiqiang;Li, Shiyue;Yi, Huimin;Xiang, Andy Peng
Mesenchymal stromal cells (MSCs) have been considered a promise alternative for treatment of acute respiratory distress syndrome (ARDS). However, there is significant heterogeneity in their therapeutic efficiency, largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs. Here, we hypothesize that the cholinergic anti-inflammatory pathway (CAP), which is recognized as a neuroimmunological pathway, may be包括在治疗机制中减轻脂多糖（LPS）和自由基肺部感染模型的机制，我们发现炎症细胞浸润和蓝色渗漏降低了，胆碱乙酰基酯（CHAT）和囊泡乙酰乙基胆汁液的表达水平被阻塞或α7烟碱使用了乙酰胆碱（ACH）受体（α7NACHR） - 敲除小鼠，MSC的治疗作用显着降低，表明CAP在MSC的影响中可能在ARDS治疗中起重要作用。那个球烟碱能受体令人兴奋的刺激性，可以减轻肺部炎症并减轻临床研究中ARDS患者的呼吸道症状（CHICTR2100047403，我们在综合中揭示了先前未识别的MSC激活机制，该方法是限制了MSC的临床策略，以示为MSCS SSCSS SUPTINE cAPTIRE cAPTIRE cAPTIRESSICTIONS类似的综合症。患有患者ARDS。
Mesenchymal stromal cells (MSCs) have been considered a promising alternative for treatment of acute respiratory distress syndrome (ARDS). However, there is significant heterogeneity in their therapeutic efficacy, largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs. Here, we hypothesize that the cholinergic anti-inflammatory pathway (CAP), which is recognized as a neuroimmunological pathway, may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS. Using lipopolysaccharide (LPS) and bacterial lung inflammation models, we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) in lung tissue were significantly increased 6 hours after MSC infusion. When the vagus nerve was blocked or α7 nicotinic acetylcholine (ACh) receptor (α7nAChR)-knockout mice were used, the therapeutic effects of MSCs were significantly reduced, suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment. Our results further showed that MSC-derived prostaglandin E2 (PGE2) likely promoted ACh synthesis and release. Additionally, based on the efficacy of nAChR and α7nAChR agonists, we found that lobeline, the nicotinic cholinergic receptor excitation stimulant, may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study (ChiCTR2100047403). In summary, we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome, providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.
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DOI：
10.1073/pnas.1522905113
发表时间：
2016-01-05
影响因子：
11.1
作者：
Ko, Jung Hwa;Lee, Hyun Ju;Oh, Joo Youn
通讯作者：
Oh, Joo Youn
影响因子：
2.3
作者：
Li, Kun-Cheng;Ho, Yu-Ling;Huang, Guan-Jhong
通讯作者：
Huang, Guan-Jhong
影响因子：
2.5
作者：
Lim, Hee-Don;Kim, Ki-Joong;Namgung, Uk
通讯作者：
Namgung, Uk
影响因子：
3.7
作者：
Revathikumar P;Estelius J;Karmakar U;Le Maître E;Korotkova M;Jakobsson PJ;Lampa J
通讯作者：
Lampa J
影响因子：
12.3
作者：
Chandrasekharan NV;Simmons DL
通讯作者：
Simmons DL