title: Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB.
abstract: 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-kappaB 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-kappaB as a key regulator of M2-driven inflammatory reactions in vitro and in vivo. p50 NF-kappaB inhibits NF-kappaB-driven, M1-polarizing, IFN-beta 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-kappaB p50 is a key component in the orchestration of M2-driven inflammatory reactions.
authors.affiliation: Fondazione Humanitas per la Ricerca, 20089 Rozzano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Porta
authors.forename: Monica
authors.initials: M
authors.lastname: Rimoldi
authors.forename: Geert
authors.initials: G
authors.lastname: Raes
authors.forename: Lea
authors.initials: L
authors.lastname: Brys
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
authors.forename: Diana
authors.initials: D
authors.lastname: Di Liberto
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.forename: Serena
authors.initials: S
authors.lastname: Ghisletti
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Natoli
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Antonio
authors.initials: A
authors.lastname: Sica
mesh_terms: D000818:Animals; D016764:Cell Polarity; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D016899:Interferon-beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000172:deficiency / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D016899:Interferon-beta
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