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 D-3 (1,25-(OH)(2)D-3) on the expre ssion of macrophage colony-stimulating factor (M-CSF), leukemia inhibi tory factor (LIF), and turner necrosis factor-alpha (TNF-alpha) genes in primary rat astrocytes and C6 glioma cells was examined, The result s show that the hormone differentially regulates the cytokine mRNA in the two cell types, 1,25-(OH)(2)D-3 augments M-CSF and LIF mRNA in C6 glioma cells, while lipopolysaccharide (LPS) has minimal effects, When LPS and 1,25-(OH)(2)D-3 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 stimul us conditions used, In contrast, 1,25-(OH)(2)D-3 has no pronounced eff ect on M-CSF, LIF, and TNF-alpha transcripts in primary astrocytes whe n used as a sole stimulus, while treatment with LPS strongly enhances the levels of the three cytokines, However, when 1,25-(OH)(2)D-3 is us ed 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 regula tory mechanisms in C6 cells and in primary astrocytes, They also sugge st that 1,25-(OH)(2)D-3, by altering the response of astrocytes to an inflammatory stimulus, could participate in the regulation of the CNS immune response. (C) 1996 Wiley-Liss, Inc.