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.

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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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