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In vitro phenotypic effects of Lipoxin A4 on M1 and M2 polarized macrophages derived from THP-1

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Abstract

Background

Lipoxin A4 (LXA4) is a specialized pro-resolving mediator involved in the resolution phase of inflammation that is crucial for the return of tissues to homeostasis, healing, and regenerative processes. LXA4 can modify the microenvironment via its receptor, formyl peptide receptor 2 (FPR2) and thus modulate the inflammatory response. However, the effect of exogeneous LXA4 application on polarized macrophages remains unstudied. The objective of this study was to assess the effect of LXA4 on macrophage activity and on the phenotype modulation of polarized M1 and M2 macrophages derived from THP-1 monocytes.

Methods and results

Once differentiated, human macrophages were incubated with interleukin 4 (IL-4) and IL-13 to obtain M2-polarized macrophages or with interferon gamma and lipopolysaccharide for classical macrophage activation. The mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages. LXA4 (0–100 nM) did not affect the viability of M1 and M2 macrophages or the phagocytic activity of these cells. Gene expression of FPR2, referred as a receptor for the LXA4, was higher in M1 compared with M2, and was not modified by the LXA4 at the doses used. Moreover, LXA4 exhibited anti-inflammatory properties illustrated by the decreasing in the gene expression of pro-inflammatory cytokines (IL-6, tumor necrosis factor alpha, IL-1β) in M1 and by the increase in the expression of anti-inflammatory cytokines (IL-10) in M2 macrophages.

Conclusions

These results provide new insights regarding the potential of LXA4 to regulate the polarization state of macrophages.

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Funding

This research was funded by the Agence Nationale de la Recherche (ANR), grant number ANR-19-CE19-0006.

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Authors and Affiliations

  1. Nantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229, 44000, Nantes, France

    Davy Aubeux, Solène Tessier, Fabienne Pérez, Valérie Geoffroy & Alexis Gaudin

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  1. Davy Aubeux
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  2. Solène Tessier
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  3. Fabienne Pérez
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  4. Valérie Geoffroy
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  5. Alexis Gaudin
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Contributions

DA, ST, AG Planned and designed the research. DA, ST, AG Wrote the manuscript. ST Performed experiments. DA, ST, AG Performed experiments and analyzed data. VG, FP Analyzed data. All authors read and approved the final manuscript.

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Correspondence to Alexis Gaudin.

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The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Aubeux, D., Tessier, S., Pérez, F. et al. In vitro phenotypic effects of Lipoxin A4 on M1 and M2 polarized macrophages derived from THP-1. Mol Biol Rep 50, 339–348 (2023). https://doi.org/10.1007/s11033-022-08041-5

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  • DOI: https://doi.org/10.1007/s11033-022-08041-5

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