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

BACKGROUND: AKT3 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. METHODS: The mRNA level of AKT3, Data from The Cancer Geno...

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Autores principales: Zhu, Youfeng, Chen, Yang, Xie, Di, Xia, Dong, Kuang, Huanming, Guo, Xinmin, Ning, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507695/
https://www.ncbi.nlm.nih.gov/pubmed/37731502
http://dx.doi.org/10.3389/fimmu.2023.1260584
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author Zhu, Youfeng
Chen, Yang
Xie, Di
Xia, Dong
Kuang, Huanming
Guo, Xinmin
Ning, Bo
author_facet Zhu, Youfeng
Chen, Yang
Xie, Di
Xia, Dong
Kuang, Huanming
Guo, Xinmin
Ning, Bo
author_sort Zhu, Youfeng
collection PubMed
description BACKGROUND: AKT3 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. METHODS: The 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. RESULTS: AKT3 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. CONCLUSION: Collectively, 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 pubmed-105076952023-09-20 Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia Zhu, Youfeng Chen, Yang Xie, Di Xia, Dong Kuang, Huanming Guo, Xinmin Ning, Bo Front Immunol Immunology BACKGROUND: AKT3 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. METHODS: The 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. RESULTS: AKT3 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. CONCLUSION: Collectively, 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. Frontiers Media S.A. 2023-09-05 /pmc/articles/PMC10507695/ /pubmed/37731502 http://dx.doi.org/10.3389/fimmu.2023.1260584 Text en Copyright © 2023 Zhu, Chen, Xie, Xia, Kuang, Guo and Ning https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhu, Youfeng
Chen, Yang
Xie, Di
Xia, Dong
Kuang, Huanming
Guo, Xinmin
Ning, Bo
Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507695/
https://www.ncbi.nlm.nih.gov/pubmed/37731502
http://dx.doi.org/10.3389/fimmu.2023.1260584
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