Role of SOCS3 in enhanced acute-phase protein genes by neonatal macrophages in response to IL-6

Role of SOCS3 in enhanced acute-phase protein genes by neonatal macrophages in response to IL-6
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SOCS3 在新生儿巨噬细胞响应 IL-6 增强急性期蛋白基因中的作用

DOI:
10.1016/j.jmii.2019.05.005
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发表时间:
2021-04-22
影响因子:
7.4
通讯作者:
Chen, Tong-Xin
Chen, Tong-Xin
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Xia-Fang;Wu, Jing;Chen, Tong-Xin

文献摘要

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背景:白细胞介素6(IL-6)诱导的炎症反应与新生儿的发病率和死亡率直接相关。本研究旨在通过对IL-6/STAT 3信号通路的研究,探讨IL-6在新生儿炎症反应中的作用机制。方法:采集健康足月新生儿脐带血和健康志愿者外周静脉血。分离成人和脐带血单核细胞并诱导为巨噬细胞。然后在IL-6刺激前用或不用MG 132预处理巨噬细胞。蛋白质分析采用Western blot,mRNA分析采用真实的时间PCR,膜分子分析采用流式细胞术。结果:新生儿巨噬细胞经IL-6刺激后,其急性时相蛋白基因的表达明显高于成人巨噬细胞。在新生巨噬细胞中观察到STAT 3的磷酸化显著增强。SOCS 3在新生巨噬细胞中的mRNA和蛋白表达均低于成年巨噬细胞。MG 132预处理后,SOCS 3蛋白表达增加,STAT 3磷酸化水平降低,APP基因表达减弱。结论:新生儿表现出下游靶基因和IL-6/STAT 3信号通路的表达增强,这与SOCS 3减少有关。这为研究新生儿的炎症反应提供了新的视角。Copyrightª 2019,Taiwan Society of Microbiology.出版社:Elsevier Taiwan LLC这是一个在CC BY-NC-ND许可证下的开放获取文章(http://creativecommons.org/licenses/by-nc-nd/4.0/)。
Background: Interleukin 6 (IL-6) induce the inflammatory response directly related with the morbidity and mortality of neonatal. Here we aimed to explore the mechanism of IL-6 in neonatal inflammatory response by studying the IL-6/STAT3 signaling pathway. Methods: Cord blood samples from health term neonatal and peripheral venous blood from health volunteers were collected. The monocytes of adults and cord blood were isolated and induced into macrophages. Then the macrophages were pretreated with or without MG132 before IL-6 stimulation. Proteins were analyzed by Western blot, mRNA by real time PCR and membrane molecule by flow cytometry. Results: The acute phase protein gene expression in neonatal macrophages after stimulated with IL-6 were higher than that in adult. Significantly enhanced phosphorylation of STAT3 was seen in neonatal macrophages. Both mRNA and protein expression of SOCS3 in neonatal macrophages were lower than that in adult. After pretreated with MG132, the expression of SOCS3 protein was increased which lead to attenuate the STAT3 phosphorylation and APP gene expression. Conclusion: Neonatal exhibit an enhanced expression of downstream target genes and IL-6/ STAT3 signal pathway which is related with the diminished SOCS3. This provides a new sight into inflammatory responses in neonatal. Copyright & ordf; 2019, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).