title: IL-1β and TNFα promote monocyte viability through the induction of GM-CSF expression by rheumatoid arthritis synovial fibroblasts.
abstract: BACKGROUND
  Macrophages and synovial fibroblasts (SF) are two major cells implicated in the pathogenesis of rheumatoid arthritis (RA). SF could be a source of cytokines and growth factors driving macrophages survival and activation. Here, we studied the effect of SF on monocyte viability and phenotype.
  
  
  METHODS
  SF were isolated from synovial tissue of RA patients and CD14+ cells were isolated from peripheral blood of healthy donors. SF conditioned media were collected after 24 hours of culture with or without stimulation with TNFα or IL-1β. Macrophages polarisation was studied by flow cytometry.
  
  
  RESULTS
  Conditioned medium from SF significantly increased monocytes viability by 60% compared to CD14+ cells cultured in medium alone (P < 0.001). This effect was enhanced using conditioned media from IL-1β and TNFα stimulated SF. GM-CSF but not M-CSF nor IL34 blocking antibodies was able to significantly decrease monocyte viability by 30% when added to the conditioned media from IL-1β and TNFα stimulated SF (P < 0.001). Finally, monocyte cultured in presence of SF conditioned media did not exhibit a specific M1 or M2 phenotype.
  
  
  CONCLUSIONS
  Overall, rheumatoid arthritis synovial fibroblasts stimulated with proinflammatory cytokines (IL-1β and TNFα) promote monocyte viability via GM-CSF but do not induce a specific macrophage polarization.
authors.affiliation: INSERM, UMR 957, 44035 Nantes, France ; Rheumatology Unit, Nantes University Hospital, 44093 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Darrieutort-Laffite
authors.affiliation: INSERM, UMR 957, 44035 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.
authors.forename: Marie-Astrid
authors.initials: MA
authors.lastname: Boutet
authors.affiliation: INSERM, UMR 957, 44035 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.
authors.forename: Mathias
authors.initials: M
authors.lastname: Chatelais
authors.affiliation: INSERM, UMR 957, 44035 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Brion
authors.affiliation: INSERM, UMR 957, 44035 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blanchard
authors.affiliation: INSERM, UMR 957, 44035 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.affiliation: INSERM, UMR 957, 44035 Nantes, France ; Rheumatology Unit, Nantes University Hospital, 44093 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Le Goff
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000473:pathology*; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; C529076:IL34 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor