Rapamycin antagonizes interleukin-6 mediated growth arrest and differentiation of myeloblastic M1 cells

The immunosuppressant rapamycin is known to be a potent inhibitor of cytokine driven proliferation of T-lymphocytes and other cell types. Here we have examined the effect of rapamycin on the myeloblastic cell line M1 which responds to interleukin-6 (IL-6) with growth arrest and monocytoid differenti...

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Bibliographic Details
Published in:Immunology letters 1997-11, Vol.59 (2), p.115-119
Main Authors: Kloke, Otto, Kummer, Gerhard, Seeber, Siegfried
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - drug effects
Cell Division - drug effects
Growth Inhibitors - antagonists & inhibitors
Growth Inhibitors - pharmacology
Hematopoietic Stem Cells - cytology
Humans
Interleukin-6
Interleukin-6 - antagonists & inhibitors
Interleukin-6 - pharmacology
M1 cells
Macrophage-1 Antigen - biosynthesis
Mice
Monocytes - cytology
Polyenes - pharmacology
Rapamycin
Receptors, Interleukin-6
Sirolimus
Tacrolimus - analogs & derivatives
Tacrolimus - pharmacology
Tumor Cells, Cultured
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Summary:The immunosuppressant rapamycin is known to be a potent inhibitor of cytokine driven proliferation of T-lymphocytes and other cell types. Here we have examined the effect of rapamycin on the myeloblastic cell line M1 which responds to interleukin-6 (IL-6) with growth arrest and monocytoid differentiation. Single-agent rapamycin led to a retardation of M1 cell growth. In spite of this intrinsic antiproliferative effect, rapamycin was found to abrogate IL-6 induced growth arrest. Concomitant exposure to rapamycin and IL-6 also reduced the extent of monocytoid differentiation as compared to treatment with IL-6 alone. Excess levels of the FK-506 analogue ascomycin reversed the antagonistic effect of rapamycin on IL-6 mediated growth suppression, suggesting that this biological action of rapamycin is mediated by a rapamycin/immunophilin complex. The findings demonstrate that rapamycin can also act as an antagonist of cytokine induced growth arrest and differentiation.
ISSN:0165-2478
1879-0542
DOI:10.1016/S0165-2478(97)00110-7