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 inhibitory factor (LIF) upregulate membrane IL-6 receptor alpha (IL-6Ralpha) on OPM-2 myeloma cell line at transcriptional level. In OPM-2 cells, IL-6, OSM and 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-6Ralpha 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-6Ralpha upregulation was also inhibited by wortmannin, an inhibitor of the PI 3-kinase pathway. In conclusion, IL-6 can upregulate its own receptor on OPM-2 cells probably through the JAK/STAT and PI 3-kinase pathways.
Thabard
W
W
Institut de Biologie, INSERM U463, 9 quai Moncousu, Nantes cedex 01, 44093, France.
Collette
M
M
Mellerin
M P
MP
Puthier
D
D
Barillé
S
S
Bataille
R
R
Amiot
M
M
D000730:Androstadienes / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015152:Blotting, Northern; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D015850:Interleukin-6 / Q000378:metabolism*; D053614:Janus Kinase 2; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases; D009101:Multiple Myeloma / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation; D000077191:Wortmannin
D000730:Androstadienes; D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006131:Growth Inhibitors; D015850:Interleukin-6; D053614:Janus Kinase 2; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D020928:Mitogen-Activated Protein Kinases; D053683:Oncostatin M; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D019947:Receptors, Interleukin-6; D020032:Tyrphostins; D000077191:Wortmannin; C507837:LIF protein, human; C508351:OSM protein, human; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C507924:JAK2 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one