TGF-BETA-INDUCED MACROPHAGE-COLONY-STIMULATING FACTOR GENE-EXPRESSIONIN VARIOUS MESENCHYMAL CELL-LINES

We report here that transforming growth factor-beta (TGF-beta) can inc rease the expression level of macrophage colony-stimulating factor (M- CSF) mRNA in a variety of mesenchymal cell lines derived from osteobla sts, bone marrow stromal cells, fibroblasts, and myoblasts. The M-CSF activity in the conditioned medium of mouse osteoblast-like MC3T3-E1 c ells was increased by TGF-beta as well as interleukin-1 (IL-1) treatme nt. The increase of M-CSF mRNA expression was observed as early as 2 h after TGF-beta or IL-1 addition and was superinduced by cycloheximide treatment. Nuclear run-off assays revealed that the increase in M-CSF mRNA by TGF-beta as well. as IL-1 occurred, at least in part, at the transcriptional level. Platelet-derived growth factor (PDGF) also enha nced the M-CSF production in MC3T3-E1 cells. Furthermore, TGF-beta and IL-1 distinctly induced both PDGF-A and PDGF-B chain mRNA in MC3T3-E1 with different time courses. Our present studies suggest that PDGF au tocrine loop-dependent and loop-independent pathways could modulate th e M-CSF production stimulated by TGF-beta or IL-1 and account for the complexity of the cytokine network involving M-CSF in vivo under vario us physiological and pathological conditions.