DMSO reduces CSF-1 receptor levels and causes apoptosis in v-myc immortalized mouse macrophages

Abstract

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.