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Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Giuliani, Nicola Colla, Simona Sala, Roberto Moroni, Matteo Lazzaretti, Mirca Monica, Silvia La Bonomini, Sabrina Hojden, Magda Sammarelli, Gabriella Barillé, Sophie Bataille, Régis Rizzoli, Vittorio |
| Copyright Year | 2002 |
| Abstract | The biologic mechanisms involved in the pathogenesis of multiple myeloma (MM) bone disease are not completely understood. Recent evidence suggests that T cells may regulate bone resorption through the cross-talk between the critical osteoclastogenetic factor, receptor activator of nuclear factor-kappaB ligand (RANKL), and interferon gamma (IFN-gamma) that strongly suppresses osteoclastogenesis. Using a coculture transwell system we found that human myeloma cell lines (HMCLs) increased the expression and secretion of RANKL in activated T lymphocytes and similarly purified MM cells stimulated RANKL production in autologous T lymphocytes. In addition, either anti-interleukin 6 (anti-IL-6) or anti-IL-7 antibody inhibited HMCL-induced RANKL overexpression. Consistently, we demonstrated that HMCLs and fresh MM cells express IL-7 mRNA and secrete IL-7 in the presence of IL-6 and that bone marrow (BM) IL-7 levels were significantly higher in patients with MM. Moreover, we found that the release of IFN-gamma by T lymphocytes was reduced in presence of both HMCLs and purified MM cells. Furthermore, in a stromal cell-free system, osteoclastogenesis was stimulated by conditioned medium of T cells cocultured with HMCLs and inhibited by recombinant human osteoprotegerin (OPG; 100 ng/mL to 1 microg/mL). Finally, RANKL mRNA was up-regulated in BM T lymphocytes of MM patients with severe osteolytic lesions, suggesting that T cells could be involved at least in part in MM-induced osteolysis through the RANKL overexpression. |
| File Format | PDF HTM / HTML |
| DOI | 10.1182/blood-2002-04-1121 |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/100/13/4615.full.pdf?sso-checked=true |
| PubMed reference number | 12393684 |
| Alternate Webpage(s) | https://doi.org/10.1182/blood-2002-04-1121 |
| Journal | Medline |
| Volume Number | 100 |
| Issue Number | 13 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
