title: Human endotoxin tolerance is associated with enrichment of the CD14+ CD16+ monocyte subset.
abstract: Prior exposure to lipopolysaccharides (LPS) induces a state of cell resistance to subsequent LPS restimulation, known as endotoxin tolerance, mainly by repressing the expression of pro-inflammatory cytokines. We established an endotoxin tolerance model in human monocytes Endotoxin-tolerant cells showed a decrease in IκBα degradation and diminished expression of Tumor necrosis factor (TNF) (both messenger RNA [mRNA] and protein content). The myeloid differentiation factor 88 (MyD88)/MyD88 splice variant (MyD88s) ratio, an indirect way to test the Toll-like receptor 4 (TLR4) MyD88-dependent signaling cascade, did not change in endotoxin-tolerant cells when compared to LPS-stimulated or -unstimulated ones. Remarkably, cell population analysis indicated a significant increase of the CD14+ CD16+ subset only under the endotoxin-tolerant condition. Furthermore, endotoxin-tolerant cells produced higher amounts of C-X-C motif chemokine 10 (CXCL10), a typical MyD88-independent cytokine.
authors.affiliation: Departamento de Inmunogenética y Alergia, Instituto Nacional de Enfermedades Respiratorias (INER), Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Aimée
authors.initials: A
authors.lastname: Domínguez-Nieto
authors.affiliation: Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (ICMNSZ), Mexico City, Mexico; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas (IIBM), Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zentella
authors.affiliation: Facultad de Medicina, Universidad La Salle, Mexico City, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas (IIBM), Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
authors.forename: José L
authors.initials: JL
authors.lastname: Ventura
authors.affiliation: Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (ICMNSZ), Mexico City, Mexico.
authors.forename: Sigifredo
authors.initials: S
authors.lastname: Pedraza
authors.affiliation: Departamento de Inmunogenética y Alergia, Instituto Nacional de Enfermedades Respiratorias (INER), Ismael Cosío Villegas, Mexico City, Mexico. Electronic address: velazquez_juan@outlook.com.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Velázquez
mesh_terms: D054357:Chemokine CXCL10 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054357:Chemokine CXCL10; D016207:Cytokines; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D017452:Receptors, IgG
keywords: CD14CD16; CXCL10; Endotoxin tolerance; Monocytes; MyD88; TNF; Toll-like receptor 4