6533b852fe1ef96bd12aae84
RESEARCH PRODUCT
Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor κB
Geert RaesGioacchino NatoliMonica RimoldiChiara PortaLea BrysAntonio SicaFrancesco DieliPietro GhezziSerena GhislettiAlberto MantovaniPatrick De BaetselierDiana Di Libertosubject
LipopolysaccharidesP50Macrophage polarizationRegulatorInflammationBiologyImmune toleranceMiceCell polaritymedicineImmune ToleranceMacrophageAnimalsHumansCells CulturedMice KnockoutMultidisciplinaryMacrophagesCell PolarityNF-kappa B p50 SubunitNF-kappa B p50 SubunitInterferon-betaBiological SciencesCell biologyEndotoxinsSTAT1 Transcription FactorImmunologymedicine.symptomdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-08-17 |