IL-6 upregulates its own receptor on some human myeloma cell lines

Interleukin 6 (IL-6) is the major survival factor of myeloma cells. In this study, we demonstrate that IL-6, oncostatin M (OSM) and leukemia inhibitor y factor (LIF) upregulate membrane IL-6 receptor alpha (IL-6R alpha) on OPM -2 myeloma cell line at transcriptional level. In OPM-2 cells, IL-6, OSM an d LIF induce both signal transducers and activators of transcription (STAT) , mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI 3-K) activation. We show that the cytokine-induced upregulation of IL- 6R alpha can be abolished by a janus kinase (JAK)-2 specific inhibitor, i.e . AG490, suggesting an involvement of the JAK/STAT pathway in this process. Finally, IL-6R alpha upregulation was also inhibited by wortmannin, an inh ibitor of the PI 3-kinase pathway. In conclusion, IL-6 can upregulate its o wn receptor on OPM-2 cells probably through the JAK/STAT and PI 3-kinase pa thways. (C) 2001 Academic Press.