Taxol, a microtuble-stabilizing agent, has been shown to have anti- neoplastic activity against various tumors. In addition, it has been shown that taxol resembles bacterial lipopolysaccharide (LPS) in its ability to activate macrophages. Recently, we have shown that LPS induces the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) in murine B-cell lines. In light of the similarity of taxol and LPS in their effects on macrophages, we tested whether taxol could also induce the expression of GM-CSF in B-cell lines. In the present study we used the murine B-lymphoma cell line M12.4.1. In unstimulated cells, no GM-CSF protein or mRNA was detected, whereas in taxol-stimulated cells at a concentration of 30uM, GM-CSF protein was detected in the supernatants after 24 hours and mRNA was detected 4-8 hours after stimulation. This induction of GM-CSF protein and mRNA was down-regulated by 10 ng/ml of interleukin-4 (IL-4). Chase experiments with Actinomycin D revealed that IL-4 did not affect the half-life of the taxol-induced GM-CSF cytoplasmic mRNA, nor did it alter GM-CSF gene transcription. Polymerase chain reaction (PCR) analysis of nuclear RNA, utilizing probes specific for sequences in the first intron of GM-CSF, indicated that taxol enhances accumulation of nuclear precursor RNA and that IL-4 decreases this accumulation. The present study shows a novel activity of taxol in inducing the release of the hematopoietic growth factor GM-CSF from B-cells. Since GM-CSF is known to recruit macrophages and enhance their cytotoxicity against tumor cells, our observation suggests that part of the known anti-tumor activity of taxol may be due to synergistic effects of GM-CSF activity together with direct cytotoxic actions through microtuble stabilization.
