• Carolina Cubillos-Zapata, Enrique Hernández-Jiménez, Víctor Toledano, Laura Esteban-Burgos, Irene Fernández-Ruíz, Vanesa Gómez-Piña, Carlos Del Fresno, María Siliceo, Patricia Prieto-Chinchiña, Rebeca Pérez de Diego, Lisardo Boscá, Manuel Fresno, Francisco Arnalich, and Eduardo López-Collazo.
• Tumor Immunology Laboratory, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain; Innate Immunity Group, IdiPAZ, La Paz Hospital, 28046 Madrid, Spain;
• J. Immunol. 2014 Oct 15;193(8):4195-202.

AbstractEndotoxin 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.Copyright © 2014 by The American Association of Immunologists, Inc.

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