title: Zoledronic acid modulates maturation of human monocyte-derived dendritic cells.
abstract: Zoledronic acid (ZA) is a drug of the bisphosphonate class, which is widely used for the treatment of both osteoporosis and skeletal metastasis. Besides its main bone antiresorptive activity, ZA displays antitumor properties, by triggering the expansion and activation of γδ T-cells, which exert an antitumor effect through dendritic cells (DCs). Several studies have reported the interaction between ZA and γδ T-cells, but the potential immunoregulatory activity of this drug on DCs has scarcely been investigated. Therefore, in this paper, we evaluated the effects of a therapeutic dose of ZA on the in vitro generation and maturation of DCs derived from peripheral blood monocytes of healthy adult donors. We demonstrate that ZA treatment did not affect DC differentiation, but inhibited DC maturation on lipopolysaccharide activation, as shown by the impaired expression of maturation surface markers and reduced ability to induce allogeneic T-cell proliferation. Interestingly, IL-10 secretion by mature DCs was significantly lower in ZA-treated cells than in controls. We conclude that ZA exerts its immunological in vitro activity also by modulating the maturation of DCs.
authors.affiliation: Department of Surgery, University of Pisa, Pisa 56126, Italy. giulia.orsini@for.unipi.it
authors.forename: Giulia
authors.initials: G
authors.lastname: Orsini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Failli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Legitimo
authors.forename: Barbara
authors.initials: B
authors.lastname: Adinolfi
authors.forename: Antonella
authors.initials: A
authors.lastname: Romanini
authors.forename: Rita
authors.initials: R
authors.lastname: Consolini
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D004164:Diphosphonates; D007093:Imidazoles; D016753:Interleukin-10; D000077211:Zoledronic Acid