Interferon-alpha down-regulates the interleukin-6 receptor in a human multiple myeloma cell line, U266.
The effects of interferon-alpha (IFN-alpha) on the interleukin-6 (IL-6) receptor in a multiple myeloma cell line, U266, have been examined. IFN-alpha inhibits [3H]thymidine incorporation in U266 cells in a time- and dose-dependent manner. Furthermore, IFN-alpha inhibits the ability of IL-6 to induce increases in [3H]thymidine incorporation. While IFN-alpha suppresses the ability of 125I-IL-6 to bind to the IL-6 receptor on U266 cells, this effect is not due to competition of IFN-alpha with IL-6 for the IL-6 receptor. Although IFN-alpha induces IL-6 synthesis in the U266 cell, inhibition of IL-6 binding occurs when IL-6 synthesis is minimal. Furthermore, after pretreatment of U266 cells with neutralizing anti-IL-6 antibodies, IFN-alpha still inhibits 125I-IL-6 binding. These data suggest that IFN-alpha inhibition of 125I-IL-6 binding does not involve IL-6 synthesis. IFN-alpha reduces 125I-IL-6 binding without affecting its affinity, suggesting that IFN-alpha inhibits IL-6 receptor expression. Although pretreatment with cycloheximide inhibits 125I-IL-6 binding, IFN-alpha does not cause a selective decrease in the levels of gp130 or IL-6 receptor mRNA at times when 125I-IL-6 binding is inhibited. These observations indicate that IFN-alpha lowers IL-6 receptor density on U266 cells by mechanisms other than competitive binding or lowering IL-6 receptor mRNA production. Receptor down-regulation may be a mechanism of IFN-alpha-induced inhibition of growth in U266 cells.
Anthes
J C
JC
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Zhan
Z
Z
Gilchrest
H
H
Egan
R W
RW
Siegel
M I
MI
Billah
M M
MM
D002455:Cell Division; D015536:Down-Regulation; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D009101:Multiple Myeloma; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019947:Receptors, Interleukin-6; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D013936:Thymidine