IL-1β and TNFα promote monocyte viability through the induction of GM-CSF expression by rheumatoid arthritis synovial fibroblasts

Mediators Inflamm. 2014:2014:241840. doi: 10.1155/2014/241840. Epub 2014 Nov 17.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology*
  • Cell Survival
  • Cells, Cultured
  • Culture Media, Conditioned
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / metabolism*
  • Interleukins / metabolism
  • Macrophage Colony-Stimulating Factor / metabolism
  • Monocytes / immunology*
  • Monocytes / pathology*
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Culture Media, Conditioned
  • IL34 protein, human
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor