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

Youfeng Zhu; Yang Chen; Di Xie; Dong Xia; Huanming Kuang; Xinmin Guo; Bo Ning

doi:10.3389/fimmu.2023.1260584

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

Front Immunol. 2023 Sep 5:14:1260584. doi: 10.3389/fimmu.2023.1260584. eCollection 2023.

Authors

Youfeng Zhu¹, Yang Chen¹, Di Xie², Dong Xia¹, Huanming Kuang¹, Xinmin Guo³, Bo Ning⁴

Affiliations

¹ Department of Intensive Care Unit, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China.
² Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Ultrasonography, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China.
⁴ Department of Neurosurgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China.

Abstract

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.

Keywords: Akt3; VAP; immunomodulation; lung cancer; macrophage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Epithelial Cells
Humans
Lung Injury*
Lung Neoplasms*
Macrophages
Pneumonia, Ventilator-Associated*
Proto-Oncogene Proteins c-akt

Substances

AKT3 protein, human
Proto-Oncogene Proteins c-akt

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Health Science and Technology Project of Guangzhou Municipal Health Commission (20201A011022) and Research-oriented Hospital Program of Guangzhou (RHPG05). The funding body was not involved in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.