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Twist2通过FOXO1调节线粒体通透性转换来减轻NLRP3诱导的小儿肺炎炎症。

Twist2 Reduced NLRP3-Induced Inflammation of Infantile Pneumonia via Regulation of Mitochondrial Permeability Transition by FOXO1.

作者信息

Ding Niu, Liu Dian, Duan Xiaojun, Zhang Jin, Ma Song, Chen Yanping

机构信息

Department of Respiratory Medicine, Hunan Children's Hospital, Changsha, China.

Graduate Department of the Third Xiangya Hospital, Central South University, Changsha, China.

出版信息

Int Arch Allergy Immunol. 2022;183(10):1098-1113. doi: 10.1159/000525063. Epub 2022 Jun 14.

DOI:10.1159/000525063
PMID:35700708
Abstract

BACKGROUND

Infantile pneumonia is an acute inflammatory lesion of the lung caused by mycoplasma pneumonia. Indeed, Twist2 signaling pathway controls inflammatory reaction, oxidative stress, and other biological reaction. However, the regulation of Twist2 on the inflammation in infantile pneumonia remains unclear. This study explained that the function and mechanism of Twist2 in infantile pneumonia.

METHODS

The subjects included the serum samples of 12 patients with infantile pneumonia and normal healthy volunteers from Hunan Children's Hospital. Besides, mice were given with lipopolysaccharide (LPS) into the lung. Moreover, RAW264.7 macrophages were stimulated with LPS for 4 h and added to the culture medium.

RESULTS

In present study, in serum of patients with infantile pneumonia or lung tissue of mice model with infantile pneumonia, TWIST2 expression was lessened. Apart from that, TWIST2 protein could reduce the inflammatory reaction in mice model with infantile pneumonia, resulting in an inhibition in lung injury. Conversely, over-expression of TWIST2 also decreased inflammatory reaction in macrophages model via the regulation of FOXO1/NLRP3 pathway. Downregulation of TWIST2 promoted the inflammation in macrophages model by the regulation of FOXO1/NLRP3 pathway.

CONCLUSION

According to the findings, present study have identified that the TWIST2 could reduce the inflammation of infantile pneumonia by NLRP3 inflammasome through the regulation of mitochondrial permeability transition and the induction of FOXO1 expression.

摘要

背景

小儿肺炎是由支原体肺炎引起的肺部急性炎症性病变。事实上,Twist2信号通路控制炎症反应、氧化应激及其他生物学反应。然而,Twist2对小儿肺炎炎症的调控仍不清楚。本研究阐述了Twist2在小儿肺炎中的作用及机制。

方法

研究对象包括来自湖南省儿童医院的12例小儿肺炎患者的血清样本和正常健康志愿者。此外,给小鼠肺内注射脂多糖(LPS)。而且,用LPS刺激RAW264.7巨噬细胞4小时后加入培养基中。

结果

在本研究中,小儿肺炎患者血清或小儿肺炎小鼠模型的肺组织中,TWIST2表达降低。除此之外,TWIST2蛋白可减轻小儿肺炎小鼠模型中的炎症反应,从而抑制肺损伤。相反,TWIST2的过表达也通过调节FOXO1/NLRP3途径降低巨噬细胞模型中的炎症反应。TWIST2的下调通过调节FOXO1/NLRP3途径促进巨噬细胞模型中的炎症反应。

结论

根据研究结果,本研究已确定TWIST2可通过NLRP3炎性小体,通过调节线粒体通透性转换和诱导FOXO1表达来减轻小儿肺炎的炎症。

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