Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia

BackgroundAKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia.MethodsThe mRNA level of AKT3, Data from The Cancer Genome At...

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Main Authors: Youfeng Zhu, Yang Chen, Di Xie, Dong Xia, Huanming Kuang, Xinmin Guo, Bo Ning
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260584/full
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author Youfeng Zhu
Yang Chen
Di Xie
Dong Xia
Huanming Kuang
Xinmin Guo
Bo Ning
author_facet Youfeng Zhu
Yang Chen
Di Xie
Dong Xia
Huanming Kuang
Xinmin Guo
Bo Ning
author_sort Youfeng Zhu
collection DOAJ
description BackgroundAKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia.MethodsThe mRNA level of AKT3, Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The data is analyzed using the Xiantao academic analysis tool. Additionally, the roles of AKT3 in ventilator-associated pneumonia (VAP) were investigated through in vivo experiments.ResultsAKT3 was differentially expressed in various normal and tumor tissues. Functional enrichment analysis indicated the immunomodulatory function and inflammatory response of AKT3 in lung cancer. Depletion of macrophages protected against lung epithelial cells and significantly decreased MMP9, MMP19, FTH, and FTL expression levels and increased GPX4 expression levels, while partially reversing the changes in macrophage. Mechanistically, macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP.ConclusionCollectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP.
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spelling doaj.art-db570a75acab4a5e95992dc22d74f3642023-09-05T06:58:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12605841260584Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumoniaYoufeng Zhu0Yang Chen1Di Xie2Dong Xia3Huanming Kuang4Xinmin Guo5Bo Ning6Department of Intensive Care Unit, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, ChinaDepartment of Intensive Care Unit, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, ChinaDepartment of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Intensive Care Unit, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, ChinaDepartment of Intensive Care Unit, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, ChinaDepartment of Ultrasonography, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, ChinaBackgroundAKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia.MethodsThe mRNA level of AKT3, Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The data is analyzed using the Xiantao academic analysis tool. Additionally, the roles of AKT3 in ventilator-associated pneumonia (VAP) were investigated through in vivo experiments.ResultsAKT3 was differentially expressed in various normal and tumor tissues. Functional enrichment analysis indicated the immunomodulatory function and inflammatory response of AKT3 in lung cancer. Depletion of macrophages protected against lung epithelial cells and significantly decreased MMP9, MMP19, FTH, and FTL expression levels and increased GPX4 expression levels, while partially reversing the changes in macrophage. Mechanistically, macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP.ConclusionCollectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260584/fulllung cancerAkt3macrophageimmunomodulationVAP
spellingShingle Youfeng Zhu
Yang Chen
Di Xie
Dong Xia
Huanming Kuang
Xinmin Guo
Bo Ning
Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia
Frontiers in Immunology
lung cancer
Akt3
macrophage
immunomodulation
VAP
title Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia
title_full Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia
title_fullStr Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia
title_full_unstemmed Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia
title_short Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia
title_sort macrophages depletion alleviates lung injury by modulating akt3 gxp4 following ventilator associated pneumonia
topic lung cancer
Akt3
macrophage
immunomodulation
VAP
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260584/full
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