DMSO reduces CSF-1 receptor levels and causes apoptosis in v-myc immortalized mouse macrophages.
We have investigated the antiproliferative potentialof dimethyl sulfoxide (DMSO) on v-myc immortalized mouse macrophages on account of the cytotoxic effect induced by DMSO on myeloid cells. DMSO caused significant apoptosis in two immortalized macrophage celllines constitutively secreting colony-stimulating factor 1 (CSF-1). In contrast to the results described for mouse erythroleukemia cells, DMSO did not markedly decrease the level of the Spi-1/PU.1 transcription factor. However, DMSO caused a specific reduction in the protein level of the CSF-1 receptor (CSF-1R) compared to the FcgammaRIIIA immunoglobulin receptor, v-myc, and beta-actin proteins. To investigate if the level of CSF-1R might inversely correlate with DMSO-induced cell death, we derived a macrophage culture (named DN-11) that could be cultured in the presence of DMSO. Immunoblot analysis of DN-11, grown with or without DMSO, revealed significant amounts of CSF-1R under both conditions, suggesting a pivotal role for CSF-1R in the survival of DMSO-treated macrophages. Therefore, in these cells, DMSO seems to trigger apoptosis by interrupting an autocrine survival loop involving the CSF-1 receptor.
Centre of Cellular and Molecular Pharmacology, Milan, I-20129, Italy.
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P
Marthyn
A
A
Beuscart
J
J
Coll
F
F
Moreau-Gachelin
M
M
Righi
D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D015536:Down-Regulation; D016259:Genes, myc / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1
D004121:Dimethyl Sulfoxide; D011518:Proto-Oncogene Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1