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Inflammation

pp 1–11 | Cite as

PP2ACα of Alveolar Macrophages Is a Novel Protective Factor for LPS-Induced Acute Respiratory Distress Syndrome

  • Zhixing He
  • Lijun Du
  • Yuehai Ke
  • Chengping WenEmail author
  • Yun ZhangEmail author
ORIGINAL ARTICLE

Abstract

Protein phosphatase 2A (PP2A) is one main serine/threonine phosphatase in eukaryotes, and its activation changes have been linked to modulation of numerous pathological processes, such as cancer, inflammation, fibrosis, and neurodegenerative diseases. Acute respiratory distress syndrome (ARDS), the major cause of respiratory failure, remains with limited therapies available up to now. Alveolar macrophages (AMs) are essential to innate immunity and host defense, participating in the pathogenesis of ARDS. As a result, AMs are considered as a potential therapeutic target for ARDS. In our study, we firstly found that PP2A activity was significantly decreased in the lipopolysaccharide (LPS)-stimulated AMs. Furthermore, adoptive transfer of AMs with enhanced PP2A enzyme activity that was improved by C2-ceramide prior to LPS exposure alleviated acute lung inflammation. Conversely, AM-specific ablation of PP2ACα exacerbated inflammatory responses to LPS. Mechanistically, PP2ACα negatively regulates LPS-induced cytokine secretion of AMs by NF-κB and MAPK pathways. Together, these findings provide the evidence to guide the development of novel therapeutic options targeting PP2ACα for ARDS/acute lung injury.

KEY WORDS

PP2ACα Alveolar macrophages C2-ceramide Acute respiratory distress syndrome 

Notes

Acknowledgements

We thank Dr. Xiang Gao (Nanjing University, Nanjing, China) for the PP2ACαf/f mice and Dr. Ximei-Wu (Zhejiang University, Hangzhou, China) for the LysMcre mice.

Author Contributions

H.Z., L.J., C.P., Y.K., and Y.Z. designed research; H.Z., L.J., and Y.Z. performed experiments, collected and analyzed data. H.Z. and Y.Z. wrote the paper; C.P. and Y.Z. critically revised the manuscript.

Funding Information

This work was supported by The National Natural Science Foundation of China 81700022 to Y.Z., The National Key Research and Development Plan 2018YFC1705500 to C.P., Research fund of Zhejiang Chinese Medical University 111100E013/001/001/029 and 111100E013/001/001/066 to Y.Z.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Basic Research in Clinical Medicine, College of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhouChina
  2. 2.Department of Pathology and PathophysiologyZhejiang University School of MedicineHangzhouChina

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