Modulation of pro-inflammatory activation of monocytes and dendritic cells by aza-bis-phosphonate dendrimer as an experimental therapeutic agent

• DOI: 10.1186/ar4546
• Publication Date: 2014-04-18T12:27:03Z
• Authors: Yannick Degboé; Séverine Fruchon; Michel Baron; Delphine Nigon; Cédric Olivier Tu...; Anne-Marie Caminade; Rémy Poupot; Alain Cantagrel; Jean-Luc Davignon
• Keywords: Phosphonate; Modulation (music); Monocyte

Abstract Introduction Our objective was to assess the capacity of dendrimer aza-bis-phosphonate (ABP) modulate phenotype monocytes (Mo) and derived dendritic cells (MoDC) activated in response toll-like receptor 4 (TLR4) interferon γ (IFN- γ) stimulation. Methods Mo ( n = 12) MoDC 11) from peripheral blood healthy donors were prepared. Cells preincubated or not for 1 hour with ABP, then incubated lipopolysaccharide (LPS; as a TLR4 ligand) (IFN-γ) 38 hours. Secretion tumor necrosis factor α (TNFα), interleukin (IL) -1, IL-6, IL-12, IL-10 IL-23 culture medium measured by enzyme-linked immunosorbent assay (ELISA) Cytokine Bead Array. Differentiation subsequent maturation nine presence LPS analyzed flow cytometry using CD80, CD86, CD83 CD1a surface expression markers. Results orientated pro-inflammatory state. In Mo, TNFα, IL-1β levels significantly lower after prior incubation ABP. MoDC, ABP promoted secretion while decreasing dramatically level IL-12. TNFα IL-6 driven impaired treatment, attested CD80 CD86. Conclusion data indicate that possesses immunomodulatory properties on human + IFN-γ stimulation model, inducing M2 alternative activation promoting tolerogenic MoDC.