Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor κB
Open accessAbstract
Cells of the monocyte–macrophage lineage play a central role in the orchestration and resolution of inflammation. Plasticity is a hallmark of mononuclear phagocytes, and in response to environmental signals these cells undergo different forms of polarized activation, the extremes of which are called classic or M1 and alternative or M2. NF-κB is a key regulator of inflammation and resolution, and its activation is subject to multiple levels of regulation, including inhibitory, which finely tune macrophage functions. Here we identify the p50 subunit of NF-κB as a key regulator of M2-driven inflammatory reactions in vitro and in vivo. p50 NF-κB inhibits NF-κB–driven, M1-polarizing, IFN-β production. Accordingly, p50-deficient mice show exacerbated M1-driven inflammation and defective capacity to mount allergy and helminth-driven M2-polarized inflammatory reactions. Thus, NF-κB p50 is a key component in the orchestration of M2-driven inflammatory reactions.
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NF-κB p65 nuclear translocation is a marker of M1 macrophages.
“NF-κB p65 nuclear translocation is a marker of M1 macrophages [49].”
From Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway (2020) · cites this paper as [49]
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- Authors
- Porta, C., Rimoldi, M., Raes, G., Brys, L., Ghezzi, P., Di Liberto, D., Dieli, F., Ghisletti, S., Natoli, G., De Baetselier, P., Mantovani, A., & Sica, A.
- Affiliations
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico, 20089 Rozzano, Italy;
- Vrije Universiteit Brussel (BE)
- Brighton and Sussex Medical School (GB)
- Dipartimento di Biopatologia e Metodologie Biochimediche, Università di Palermo, 90134 Palermo, Italy;
- University of Palermo (IT)
- IFOM (IT)
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, and Department of Molecular ad Cellular Interactions, 1050 Brussels, Belgium;
- University of Milan (IT)
- Corresponding author
- Sica, Antonio
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-09
- Volume
- 106
- Issue
- 35
- Pages
- 14978-14983
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2736429
- OpenAlex
- W2084231086
- Cited by
- 627
- References
- 4
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 28 · 2023: 30 · 2022: 47 · 2021: 45 · 2020: 29 · 2019: 33 · 2018: 42 · 2017: 41 · 2016: 39 · 2015: 51 · 2014: 47 · 2013: 46 · 2012: 31
- FWCI
- 11.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Figshare (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- NF-κB p50, NF-κB, M2 macrophage polarization, M1 macrophage polarization, monocyte/macrophage lineage, interferon-beta, inflammation resolution, allergy, helminthiasis, macrophage plasticity
- MeSH terms
- Animals, Cells, Cultured, Endotoxins, Humans, Immune Tolerance, Lipopolysaccharides, Macrophages, Cell Polarity, Interferon-beta, Mice, Knockout, STAT1 Transcription Factor, Mice, NF-kappa B p50 Subunit
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