Resveratrol decreases CD45+CD206- subtype macrophages in LPS-induced murine acute lung injury by SOCS3 signalling pathway
Resveratrol decreases CD45+CD206- subtype macrophages in LPS-induced murine acute lung injury by SOCS3 signalling pathway
复制标题
白藜芦醇通过 SOCS3 信号通路降低 LPS 诱导的小鼠急性肺损伤中 CD45( )CD206(-) 亚型巨噬细胞
DOI：
10.1111/jcmm.14680
复制
发表时间：
2019-09-27
影响因子：
5.3
通讯作者：
Zhu, Lei
中科院分区：
文献类型：
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作者：
Hu, Lu;Chen, Zhihong;Zhu, Lei
急性肺损伤/急性呼吸窘迫综合征（Acute lung injury/acute respiratory distress syndrome，ALI/ARDS）是严重威胁危重患者生命的疾病。白藜芦醇（Resveratrol，Res）是一种天然多酚类物质，对ALI动物模型具有治疗作用，但Res是否通过调节巨噬细胞表型来减轻ALI仍不清楚。在本研究中，我们用30 mg/kg Res治疗LPS诱导的小鼠ALI，并在Res治疗后48小时观察到经Res治疗的小鼠中ALI的严重程度显著降低。在RES治疗的ALI小鼠中，神经细胞浸润显著减少，伴随着较低的CD 45（+）Siglec F-表型巨噬细胞浸润，但较高的CD 45（+）Siglec F+和CD 45（+）CD 206（+）交替激活的巨噬细胞（M2细胞）群体。此外，IL-1 β和CXCL 15细胞因子的表达在治疗的小鼠中被抑制。然而，在具有骨髓细胞限制性SOCS 3缺陷的小鼠中，Res治疗没有显著减轻ALI严重程度，并且未能增加小鼠ALI中的CD 45（+）Siglec F+和CD 45（+）CD 206（+）M2亚型巨噬细胞的群体。在野生型巨噬细胞中的进一步研究表明，Res处理有效地降低了IL-6和CXCL 15的表达，并增加了IL-1，SIRT 1和SOCS 3的表达。然而，缺乏SOCS 3表达的巨噬细胞在体外对RES诱导的IL-6和CXCL 15的抑制具有抗性。因此，我们得出结论，在LPS诱导的小鼠ALI中，Res通过SOCS 3信号传导抑制CD 45（+）Siglec F-和CD 45（+）CD 206（-）M1亚型巨噬细胞。
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are life-threatening condition in critically ill patients. Resveratrol (Res), a natural polyphenol, has therapeutic effect in animal model with ALI; however, whether Res attenuates ALI through modulation of macrophage phenotypes in the animal model remains unknown. We in this study treated LPS-induced murine ALI with 30 mg/kg Res and observed significantly reduced severity of ALI in the Res-treated mice 48 hours after Res treatment. Neutrophil infiltrates were significantly reduced, accompanied with lower infiltration of CD45(+)Siglec F- phenotype macrophages, but higher population of CD45(+)Siglec F+ and CD45(+)CD206(+) alternatively activated macrophages (M2 cells) in the Res-treated mice with ALI. In addition, the expression of IL-1beta and CXCL15 cytokines was suppressed in the treated mice. However, Res treatment in mice with myeloid cell-restricted SOCS3 deficiency did not significantly attenuate ALI severity and failed to increase population of both CD45(+)Siglec F+ and CD45(+)CD206(+) M2 subtype macrophages in the murine ALI. Further studies in wild-type macrophages revealed that Res treatment effectively reduced the expression of IL-6 and CXCL15, and increased the expression of arginase-1, SIRT1 and SOCS3. However, macrophages' lack of SOCS3 expression were resistant to the Res-induced suppression of IL-6 and CXCL15 in vitro. Thus, we conclude that Res suppressed CD45(+)Siglec F- and CD45(+)CD206(-) M1 subtype macrophages through SOCS3 signalling in the LPS-induced murine ALI.