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 differentiation. Single-agent rapamycin led to a retardation of M 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.
Kloke
O
O
Department of Internal Medicine, West German Cancer Center Essen, University of Essen Medical School.
Kummer
G
G
Seeber
S
S
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D011090:Polyenes / Q000494:pharmacology*; D019947:Receptors, Interleukin-6; D020123:Sirolimus; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
D006131:Growth Inhibitors; D015850:Interleukin-6; D016177:Macrophage-1 Antigen; D011090:Polyenes; D019947:Receptors, Interleukin-6; D020123:Sirolimus; D016559:Tacrolimus; D000093242:Interleukin-6 Inhibitors; C058028:immunomycin