Differential expression of M-CSF, LIF, and TNF-alpha genes in normal and malignant rat glial cells: regulation by lipopolysaccharide and vitamin D.

The effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the expression of macrophage colony-stimulating factor (M-CSF), leukemia inhibitory factor (LIF), and tumor necrosis factor-alpha (TNF-alpha) genes in primary rat astrocytes and C6 glioma cells was examined. The results show that the hormone differentially regulates the cytokine mRNA in the two cell types. 1,25-(OH)2D3 augments M-CSF and LIF mRNA in C6 glioma cells, while lipopolysaccharide (LPS) has minimal effects. When LPS and 1,25-(OH)2D3 are used in combination, a strong synergistic effect upon the induction of M-CSF and LIF genes is observed. No TNF-alpha transcript has been detected in C6 glioma cells under any stimulus conditions used. In contrast, 1,25-(OH)2D3 has no pronounced effect on M-CSF, LIF, and TNF-alpha transcripts in primary astrocytes when used as a sole stimulus, while treatment with LPS strongly enhances the levels of the three cytokines. However, when 1,25-(OH)2D3 is used in combination with LPS, a partial reduction in LPS-induced levels of M-CSF and TNF-alpha mRNA is observed. The overall results indicate that genes coding for some inflammatory cytokines obey distinct regulatory mechanisms in C6 cells and in primary astrocytes. They also suggest that 1,25-(OH)2D3, by altering the response of astrocytes to an inflammatory stimulus, could participate in the regulation of the CNS immune response.