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Enhancing effect of sodium butyrate on phosphatidylserine–liposome-induced macrophage polarization

  • Original Research Article
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Abstract

Object

Phosphatidylserine-containing liposomes (PSLs) can mimic the immunomodulatory effects of apoptotic cells by binding to the phosphatidylserine receptors of macrophages. Sodium butyrate, an antiinflammatory short-chain fatty acid, is known to facilitate the M2 polarization of macrophages. This study aimed to investigate the effect of sodium butyrate on PSLs-induced macrophage polarization.

Methods

PSLs physical properties and cellular uptake tests, reverse transcription–quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and flow cytometry analysis were performed to assess the polarization-related indicators of M1/M2 macrophages.

Results

The results showed that sodium butyrate did not affect the size and cellular uptake of PSLs. For M1 macrophage polarization, sodium butyrate significantly intensified the antiinflammatory function of PSLs, inhibiting LPS-induced proinflammatory genes expression, cytokines and enzyme release (tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase), as well as CD86 (M1 marker) expression. In addition to the enhancing effect of antiinflammation, sodium butyrate also promoted PSL-induced M2 macrophages polarization, especially elevated thymus and activation-regulated chemokine (TARC) and arginase-1 (Arg-1) enzyme levels which are involved in tissue repair.

Conclusion

Sodium butyrate enhanced antiinflammatory properties and M2-polarization inducing effect of PSLs. Therefore, sodium butyrate may represent a novel approach to enhance PSL-induced macrophage polarization.

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Acknowledgements

The authors thank all participants for taking part in the study. Lele Wu acknowledges support from the China Scholarship Council (CSC, Grant No.201808260022).

Funding

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1A6A1A03039462) and the SNUD Research Fund (860-20190107).

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Authors and Affiliations

  1. Department of Dental Biomaterials Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 03080, South Korea

    Lele Wu, Gyeung Mi Seon, Yongjoon Kim, Sang Hoon Choi, Quang Canh Vo & Hyeong-Cheol Yang

Authors
  1. Lele Wu
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  2. Gyeung Mi Seon
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  3. Yongjoon Kim
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  4. Sang Hoon Choi
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  5. Quang Canh Vo
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  6. Hyeong-Cheol Yang
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Contributions

Conceptualization, H-CY; methodology, LLW and YK; resources, SHC and QCV; data curation, LLW and H-CY; writing—original draft preparation, H-CY; writing—review and editing, LLW and H-CY.

Corresponding author

Correspondence to Hyeong-Cheol Yang.

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Conflict of interest

The authors declare no conflicts of interest.

Ethics approval

All animal experiments in this study were performed following the guidelines of Institutional Animal Care approved by the Committee of Seoul National University (SNU-201217-4).

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Not applicable.

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All the authors have approved the manuscript for final publication.

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Responsible Editor: John Di Battista.

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Wu, L., Seon, G.M., Kim, Y. et al. Enhancing effect of sodium butyrate on phosphatidylserine–liposome-induced macrophage polarization. Inflamm. Res. 71, 641–652 (2022). https://doi.org/10.1007/s00011-022-01563-5

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  • DOI: https://doi.org/10.1007/s00011-022-01563-5

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