title: Soluble CD14 acts as a DAMP in human macrophages: origin and involvement in inflammatory cytokine/chemokine production.
abstract: The innate immune system is able to detect bacterial LPS through the pattern recognition receptor CD14, which delivers LPS to various TLR signaling complexes that subsequently induce intracellular proinflammatory signaling cascades. In a previous study, we showed the overproduction of the soluble form of CD14 (sCD14) by macrophages from patients with cystic fibrosis (CF). CF is an autosomal recessive disorder that is caused by mutations in the gene that encodes the CFTR protein and is characterized by persistent inflammation. Macrophages play a significant role in the initial stages of this disease due to their inability to act as suppressor cells, leading to chronic inflammation in CF. In this work, we investigated the origin of sCD14 by human macrophages and studied the effect of sCD14 on the production of inflammatory cytokine/chemokine. Our data indicate that sCD14 stimulate proinflammatory cytokine/chemokine production in a manner that is independent of LPS but dependent on the TLR-4/CD14 membrane complex, NF-κB, and the inflammasome. Therefore, sCD14, overproduced by CF macrophages, originates primarily from the endocytosis/exocytosis process and should be considered to be a danger-associated molecular pattern. This elucidation of the origin and inflammation-induced mechanisms associated with sCD14 contributes to our understanding of maintained tissue inflammation.-Lévêque, M., Simonin-Le Jeune, K., Jouneau, S., Moulis, S., Desrues, B., Belleguic, C., Brinchault, G., Le Trionnaire, S., Gangneux, J.-P., Dimanche-Boitrel, M.-T., Martin-Chouly, C. Soluble CD14 acts as a DAMP in human macrophages: origin and involvement in inflammatory cytokine/chemokine production.
authors.affiliation: Stress Membrane and Signaling Team, Research Institute for Environmental and Occupational Health (IRSET), INSERM Unité 1085, Rennes, France.|Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.
authors.forename: Manuella
authors.initials: M
authors.lastname: Lévêque
authors.affiliation: Stress Membrane and Signaling Team, Research Institute for Environmental and Occupational Health (IRSET), INSERM Unité 1085, Rennes, France.|Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Simonin-Le Jeune
authors.affiliation: Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.|Chemical Contaminant Immunity and Inflammation Team, Research Institute for Environmental and Occupational Health (IRSET), INSERM Unité 1085, Rennes, France.|Centre de Ressource et de Compétences de la Mucoviscidose, Centre Hospitalier Universitaire de Rennes, Rennes, France; and.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jouneau
authors.affiliation: Stress Membrane and Signaling Team, Research Institute for Environmental and Occupational Health (IRSET), INSERM Unité 1085, Rennes, France.|Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.
authors.forename: Solenn
authors.initials: S
authors.lastname: Moulis
authors.affiliation: Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.|Centre de Ressource et de Compétences de la Mucoviscidose, Centre Hospitalier Universitaire de Rennes, Rennes, France; and.|Chemistry, Oncogenesis, Stress and Signaling (COSS), Centre Eugène Marquis, INSERM Unité 1242, Rennes, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Desrues
authors.affiliation: Centre de Ressource et de Compétences de la Mucoviscidose, Centre Hospitalier Universitaire de Rennes, Rennes, France; and.
authors.forename: Chantal
authors.initials: C
authors.lastname: Belleguic
authors.affiliation: Centre de Ressource et de Compétences de la Mucoviscidose, Centre Hospitalier Universitaire de Rennes, Rennes, France; and.
authors.forename: Graziella
authors.initials: G
authors.lastname: Brinchault
authors.affiliation: Stress Membrane and Signaling Team, Research Institute for Environmental and Occupational Health (IRSET), INSERM Unité 1085, Rennes, France.|Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Trionnaire
authors.affiliation: Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.|Centre de Ressource et de Compétences de la Mucoviscidose, Centre Hospitalier Universitaire de Rennes, Rennes, France; and.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gangneux
authors.affiliation: Stress Membrane and Signaling Team, Research Institute for Environmental and Occupational Health (IRSET), INSERM Unité 1085, Rennes, France.|Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Dimanche-Boitrel
authors.affiliation: Stress Membrane and Signaling Team, Research Institute for Environmental and Occupational Health (IRSET), INSERM Unité 1085, Rennes, France; corinne.chouly@univ-rennes1.fr.|Unité Mixte de Service 3480 Biosit, University of Rennes 1, Rennes, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Martin-Chouly
mesh_terms: D018925:Chemokines / Q000096:biosynthesis* / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018925:Chemokines; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B
keywords: NF-κB; cystic fibrosis; inflammasome; inflammation