title: NFκB2/p100 is a key factor for endotoxin tolerance in human monocytes: a demonstration using primary human monocytes from patients with sepsis.
abstract: Endotoxin tolerance (ET) is a state of reduced responsiveness to endotoxin stimulation after a primary bacterial insult. This phenomenon has been described in several pathologies, including sepsis, in which an endotoxin challenge results in reduced cytokine production. In this study, we show that the NFκ L chain enhancer of activated B cells 2 (NFκB2)/p100 was overexpressed and accumulated in a well-established in vitro human monocyte model of ET. The p100 accumulation in these cells inversely correlated with the inflammatory response after LPS stimulation. Knocking down NFκB2/p100 using small interfering RNA in human monocytes further indicated that p100 expression is a crucial factor in the progression of ET. The monocytes derived from patients with sepsis had high levels of p100, and a downregulation of NFκB2/p100 in these septic monocytes reversed their ET status.
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
authors.forename: Carolina
authors.initials: C
authors.lastname: Cubillos-Zapata
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernández-Jiménez
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
authors.forename: Víctor
authors.initials: V
authors.lastname: Toledano
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
authors.forename: Laura
authors.initials: L
authors.lastname: Esteban-Burgos
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
authors.forename: Irene
authors.initials: I
authors.lastname: Fernández-Ruíz
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
authors.forename: Vanesa
authors.initials: V
authors.lastname: Gómez-Piña
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain;
authors.forename: Carlos
authors.initials: C
authors.lastname: Del Fresno
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
authors.forename: María
authors.initials: M
authors.lastname: Siliceo
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), 28046 Madrid, Spain;
authors.forename: Patricia
authors.initials: P
authors.lastname: Prieto-Chinchiña
authors.affiliation: Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Laboratory of Immunogenetics of Diseases, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; and.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Pérez de Diego
authors.affiliation: Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), 28046 Madrid, Spain;
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
authors.forename: Francisco
authors.initials: F
authors.lastname: Arnalich
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; elopezc@salud.madrid.org.
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
mesh_terms: D000368:Aged; D015536:Down-Regulation; D004731:Endotoxins / Q000276:immunology*; D055786:Gene Knockout Techniques; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D052003:NF-kappa B p52 Subunit / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D018805:Sepsis / Q000276:immunology*
chemical_list: D004731:Endotoxins; D052003:NF-kappa B p52 Subunit; D034741:RNA, Small Interfering