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Interleukin-6 prevents dexamethasone-induced myeloma cell death
J Hardin, S MacLeod, I Grigorieva, R Chang, B Barlogie, H Xiao and J Epstein
Arkansas Cancer Research Center, University of Arkansas for Medical
Sciences, Little Rock 72205.
The effects of dexamethasone on the growth of four human multiple myeloma
cell lines were studied. In addition, the effects on the expression of
interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes were investigated by
the use of reverse-transcriptase polymerase chain reaction. Dexamethasone
(Dex) concentrations of 10(-7) to 10(-6) mol/L inhibited IL-6 gene
expression in three of four cell lines studied, whereas the higher
concentration of the hormone inhibited also IL-6R gene expression. Dex
effects were modulated through the glucocorticoid receptor (GR). Dex
treatment resulted in killing of sensitive cells associated with DNA
fragmentation, which could be reversed by concomitant treatment with IL-6.
The reversal of Dex-mediated effects by IL-6 did not result from an
inhibition of GR function as measured by receptor nuclear translocation or
Dex-regulated reporter gene function. These results indicate that blockage
of the IL-6 signaling pathway is essential for effective myeloma cell kill
by Dex.
Volume 84,
Issue 9,
pp. 3063-3070,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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