title: Immature dendritic cells in multiple myeloma are prone to osteoclast-like differentiation through interleukin-17A stimulation.
abstract: Interleukin 17A (IL17A), a cytokine involved in allergy, inflammation and osteoclastogenesis, was investigated in multiple myeloma (MM) to assess its role in the osteoclast (OC)-like activity of marrow immature dendritic cells (iDCs). Comparing nine MM patients with control subjects affected by monoclonal gammopathy of undetermined significance, we found high IL17A expression in the marrow plasma of MM patients in parallel with its deposits within the stromal matrix. Increased expression of the IL17A receptor (IL17RA) was also found in primary myeloma iDCs, which underwent OC-like transdifferentiation after IL17A stimulation. To assess the role of IL17A, we measured the activity of the IL17/IL17RA pathway in IL17A-transdifferentiated iDCs and the expression of functional OC genes by Western blotting and real-time polymerase chain reaction. These cells showed increased RNA transcription of genes enrolled in the maturation of OCs, while NFATC1 and FOS were induced by IL17A, independently of NFKB1 phosphorylation. Moreover, the concurrent phosphorylation of the Lip isoform of CEBPB and the down-regulation of MAFB supported the activation of IL17RA pathway in OC-like transdifferentiated iDCs that was apparently unrelated to TNFRSF11A signalling. These data emphasize the involvement of iDCs in MM hyperactive osteoclastogenesis and suggest that their bone resorption activity is also regulated, at least in vitro, by IL17RA.
authors.affiliation: Department of Biomedical Science and Clinical Oncology, University of Bari Aldo Moro, Piazza Giulio Cesare, Bari, Italy. marco.tucci@uniba.it
authors.forename: Marco
authors.initials: M
authors.lastname: Tucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Stucci
authors.forename: Annalisa
authors.initials: A
authors.lastname: Savonarola
authors.forename: Sabino
authors.initials: S
authors.lastname: Ciavarella
authors.forename: Paola
authors.initials: P
authors.lastname: Cafforio
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.forename: Franco
authors.initials: F
authors.lastname: Silvestris
mesh_terms: D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000235:genetics; D054338:Cell Transdifferentiation / Q000187:drug effects* / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17