Abstract
Lipoxin A4 (LXA4) has been shown to have anti-inflammatory activity, but its underlying molecular mechanisms are not clear. Herein, we investigated the potential role of LXA4 in macrophage polarization and elucidated its possible molecular mechanism. The RAW264.7 macrophage cell line was pretreated with LXA4 with or without lipopolysaccharides (LPSs) and interleukin-4 (IL-4). In cultured macrophages, LXA4 inhibited LPS-induced inflammatory polarization, thereby decreasing the release of proinflammatory cell factors (IL-1β, IL-6, TNF-α) and increasing the release of anti-inflammatory cytokines (IL-4 and IL-10). Notably, the inhibitory effect of LXA4 on inflammatory macrophage polarization was related to the downregulation of p-NF-κB p65 and IRF5 activity, which reduced the LPS-induced phenotypic and functional polarization of M1 macrophages via the FPR2/IRF5 signaling pathway. Moreover, LXA4 also induced the IL-4-induced polarization of M2 macrophages by promoting the FPR2/IRF4 signaling pathway. Therefore, LXA4 regulates M1/M2 polarization of macrophages via the FPR2–IRF pathway.
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Data availability
All data are available from the corresponding author upon request.
Abbreviations
- Arg-1:
-
Arginase-1
- BCA:
-
Bicinchoninic acid
- CCK-8:
-
Cell counting kit-8
- DMEM:
-
Dulbecco's modified eagle medium
- FBS:
-
Fetal bovine serum
- HRP:
-
Horseradish peroxidase
- IFN-γ:
-
Interferon-γ
- iNOS:
-
Inducible nitric oxide synthase
- IL-4:
-
Interleukin-4
- LXA4:
-
Lipoxin A4
- LPS:
-
Lipopolysaccharides
- LXs:
-
Lipoxygenins
- PVDF:
-
Polyvinylidene difluoride
- ROS:
-
Reactive oxygen species
- TLR:
-
Toll-like receptor
- CK:
-
Creatine kinase
- PNC:
-
Penicillin
- PFA:
-
Paraformaldehyde
- TF:
-
Tissue factor
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Acknowledgements
This study was sponsored by the Natural Science Foundation of Zhejiang Province, China (LY21H050005). Additionally, this study was also supported by the Wenzhou Municipal Science and Technology Project (Y2020025).
Funding
This study was sponsored by the Natural Science Foundation of Zhejiang Province, China (LY21H050005) and the Natural Science Foundation of China (81772264). Additionally, this study was also supported by the Wenzhou Municipal Science and Technology Project (Y2020025) and the Wenzhou Municipal Science and Technology Bureau (Y2020274).
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by JY, FL and LC. The first draft of the manuscript was written by JY and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Yuan, J., Lin, F., Chen, L. et al. Lipoxin A4 regulates M1/M2 macrophage polarization via FPR2–IRF pathway. Inflammopharmacol 30, 487–498 (2022). https://doi.org/10.1007/s10787-022-00942-y
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DOI: https://doi.org/10.1007/s10787-022-00942-y