Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Department of Pediatrics, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Int J Mol Sci. 2022 May 10;23(10):5295. doi: 10.3390/ijms23105295.
Excess inflammatory processes play a key detrimental role in the pathophysiology of acute lung injury (ALI). Mesenchymal stem cells (MSCs) were reported to be beneficial to ALI, but the underlying mechanisms have not been completely understood. The present study aimed to examine the involvement of MyD88−NFκB signaling in the immunomodulation of MSCs in mice with lipopolysaccharides (LPS)-induced ALI. We found that serum concentrations of IL-6, TNF-α, MCP-1, IL-1β, and IL-8 were significantly decreased at 6 h after LPS-induced ALI in the MSC group (p < 0.05). For each of the five cytokines, the serum concentration of each individual mouse in either group declined to a similar level at 48 h. The intensity of lung injury lessened in the MSC group, as shown by histopathology and lung injury scores (p < 0.001). The expressions of MyD88 and phospho-NFκB in the lung tissue were significantly decreased in mice receiving MSCs as measured by Western blotting and immunohistochemistry. Our data demonstrated that human umbilical cord-derived MSCs could effectively alleviate the cytokine storm in mice after LPS-induced ALI and attenuated lung injury. Firstly, we documented the correlation between the down-regulation of MyD88−NFκB signaling and immunomodulatory effects of MSCs in the situation of ALI.
过度的炎症反应在急性肺损伤 (ALI) 的病理生理学中起着关键的有害作用。间充质干细胞 (MSCs) 被报道对 ALI 有益，但潜在的机制尚未完全了解。本研究旨在研究 MyD88-NFκB 信号通路在脂多糖 (LPS) 诱导的 ALI 小鼠中 MSC 免疫调节中的作用。我们发现，在 LPS 诱导的 ALI 后 6 小时，MSC 组血清中 IL-6、TNF-α、MCP-1、IL-1β 和 IL-8 的浓度显著降低（p<0.05）。对于这五种细胞因子中的每一种，每组中每只老鼠的血清浓度在 48 小时后都下降到相似的水平。组织病理学和肺损伤评分显示 MSC 组的肺损伤程度减轻（p<0.001）。通过 Western blot 和免疫组化检测到，肺组织中 MyD88 和磷酸化 NFκB 的表达在接受 MSC 的小鼠中明显降低。我们的数据表明，人脐带来源的 MSC 可以有效缓解 LPS 诱导的 ALI 后小鼠的细胞因子风暴，并减轻肺损伤。首先，我们记录了在 ALI 情况下，MyD88-NFκB 信号通路下调与 MSC 免疫调节作用之间的相关性。
