INTERFERON-ALPHA DOWN-REGULATES THE INTERLEUKIN-6 RECEPTOR IN A HUMAN MULTIPLE-MYELOMA CELL-LINE, U266

被引:21
作者
ANTHES, JC
ZHAN, ZR
GILCHREST, H
EGAN, RW
SIEGEL, MI
BILLAH, MM
机构
[1] Schering-Plough Research Institute, Kenilworth
关键词
D O I
10.1042/bj3090175
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 [H-3]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 [H-3]thymidine incorporation. While IFN-alpha suppresses the ability of (l25)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 I-125-IL-6 binding. These data suggest that IFN-alpha inhibition of I-125-IL-6 binding does not involve IL-6 synthesis. IFN-alpha reduces I-125-IL-6 binding without affecting its affinity, suggesting that IFN-alpha inhibits IL-6 receptor expression. Although pretreatment with cycloheximide inhibits I-125-IL-6 binding, IFN-alpha does not cause a selective decrease in the levels of gp130 or IL-6 receptor mRNA at times when I-125- IL-6 binding is inhibited. These observations indicate that IFN-alpha-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.
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页码:175 / 180
页数:6
相关论文
共 38 条
[1]  
[Anonymous], 1989, Ann N Y Acad Sci, V557, P1
[2]   THE INTERFERONS - MECHANISMS OF ACTION AND CLINICAL-APPLICATIONS [J].
BARON, S ;
TYRING, SK ;
FLEISCHMANN, WR ;
COPPENHAVER, DH ;
NIESEL, DW ;
KLIMPEL, GR ;
STANTON, GJ ;
HUGHES, TK .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1991, 266 (10) :1375-1383
[3]   REGULATION OF INTERLEUKIN-6 RECEPTOR EXPRESSION IN HUMAN-MONOCYTES AND HEPATOCYTES [J].
BAUER, J ;
LENGYEL, G ;
BAUER, TM ;
ACS, G ;
GEROK, W .
FEBS LETTERS, 1989, 249 (01) :27-30
[4]  
BRENNING G, 1986, SCAND J HAEMATOL, V37, P280
[5]   HIGH-AFFINITY BINDING-SITES FOR HUMAN 26-KDA PROTEIN (INTERLEUKIN 6, B-CELL STIMULATORY FACTOR-II, HUMAN HYBRIDOMA PLASMACYTOMA GROWTH-FACTOR, INTERFERON-BETA-2), DIFFERENT FROM THOSE OF TYPE-I INTERFERON (ALPHA,BETA), ON LYMPHOBLASTOID-CELLS [J].
COULIE, PG ;
VANHECKE, A ;
VANDAMME, J ;
CAYPHAS, S ;
POUPART, P ;
DEWIT, L ;
CONTENT, J .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1987, 17 (10) :1435-1440
[6]   JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].
DARNELL, JE ;
KERR, IM ;
STARK, GR .
SCIENCE, 1994, 264 (5164) :1415-1421
[7]  
FALUS A, 1993, CYTOKINE, V4, P495
[8]  
GRAEVE L, 1993, CLIN INVESTIGATOR, V71, P664
[9]   INTERFERON-GAMMA INTERRUPTS AUTOCRINE GROWTH MEDIATED BY ENDOGENOUS INTERLEUKIN-6 IN RENAL-CELL CARCINOMA [J].
GRUSS, HJ ;
BRACH, MA ;
MERTELSMANN, RH ;
HERRMANN, F .
INTERNATIONAL JOURNAL OF CANCER, 1991, 49 (05) :770-773
[10]   INTERLEUKIN-6 AND THE ACUTE PHASE RESPONSE [J].
HEINRICH, PC ;
CASTELL, JV ;
ANDUS, T .
BIOCHEMICAL JOURNAL, 1990, 265 (03) :621-636