Down-regulation of SHP2 promotes neutrophil autophagy and inhibits neutrophil extracellular trap formation to alleviate asthma through the ERK5 pathway.

IF 1.5 4区 医学 Q4 IMMUNOLOGY
Central European Journal of Immunology Pub Date : 2024-01-01 Epub Date: 2024-11-12 DOI:10.5114/ceji.2024.143691
Dandan Shi, Jian Huang, Jie Wu
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引用次数: 0

Abstract

Introduction: Neutrophil autophagy and neutrophil extracellular trap (NET) formation are closely related to asthma pathogenesis. Src homology domain 2-containing protein tyrosine phosphatase 2 (SHP2) is an important regulatory factor in airway remodeling in asthma. This study aimed to explore the molecular mechanisms of SHP2 in neutrophils.

Material and methods: Peripheral blood samples were collected from healthy individuals and asthma patients. A dimethylsulfoxide-induced HL-60-driven neutrophil-like cell model was established. Neutrophil-like cells were treated with rapamycin to activate autophagy. Neutrophil-like cells or neutrophils were transfected with oe-SHP2, si-SHP2, oe-ERK5 or their negative controls.

Results: There was an abnormal increase of neutrophils in the peripheral blood of asthma patients. Neutrophil autophagy gradually decreased with the severity of asthma while the NET formation increased. Pearson's correlation analysis revealed that SHP2 was negatively correlated with BECN1 and LC3 and positively correlated with p62 and MPO. Moreover, SHP2 inhibited autophagy in neutrophil-like cells. Overexpression of ERK5 partially counteracted the inhibitory effect of interfering with SHP2 expression on NET formation in neutrophil-like cells. After interfering with SHP2 expression in neutrophils, the expression of BECN1 and LC3 were significantly increased, while dsDNA levels, MPO activity, and the expression levels of p62, cit-H3, MPO, ELANE, PADI4 and ERK5 were decreased.

Conclusions: Down-regulation of SHP2/ERK5 promoted neutrophil autophagy and inhibited NET formation. SHP2 could be a new indicator of asthma.

下调SHP2可促进中性粒细胞自噬,抑制中性粒细胞胞外陷阱形成,通过ERK5通路缓解哮喘。
中性粒细胞自噬和中性粒细胞胞外陷阱(NET)的形成与哮喘的发病密切相关。Src同源结构域2-含蛋白酪氨酸磷酸酶2 (SHP2)是哮喘气道重塑的重要调控因子。本研究旨在探讨SHP2在中性粒细胞中的分子机制。材料与方法:采集健康人及哮喘患者外周血标本。建立二甲亚砜诱导hl -60驱动的中性粒细胞样细胞模型。用雷帕霉素处理嗜中性粒细胞样细胞激活自噬。用e- shp2、si-SHP2、e- erk5或其阴性对照转染中性粒细胞样细胞或中性粒细胞。结果:哮喘患者外周血中性粒细胞异常增高。随着哮喘的严重程度,中性粒细胞自噬逐渐减少,NET形成增加。Pearson相关分析显示,SHP2与BECN1、LC3呈负相关,与p62、MPO呈正相关。此外,SHP2抑制中性粒细胞样细胞的自噬。ERK5过表达部分抵消了干扰SHP2表达对中性粒细胞样细胞NET形成的抑制作用。在中性粒细胞中干扰SHP2表达后,BECN1和LC3的表达显著升高,而dsDNA水平、MPO活性以及p62、cte - h3、MPO、ELANE、PADI4和ERK5的表达水平降低。结论:下调SHP2/ERK5可促进中性粒细胞自噬,抑制NET的形成。SHP2可能是哮喘的新指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.00
自引率
0.00%
发文量
17
审稿时长
6-12 weeks
期刊介绍: Central European Journal of Immunology is a English-language quarterly aimed mainly at immunologists.
文献相关原料
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索莱宝
Rapamycin
索莱宝
Dimethylsulfoxide
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