TGF-β is a bidirectional modulator of cytokine receptor expression on murine bone marrow cells: Differential effects of TGF-β1 and TGF-β3

Transforming growth factor β (TGF-β), an immunomodulator, has inhibitory as well as stimulatory effects on bone marrow cells. In this study, we demonstrate that TGF-β1 also is a bidirectional modulator of CSF receptor expression on murine bone marrow cells. TGF-β1 up-regulated granulocyte- macrophage (GM)-CSF receptor expression in a time- and dose-dependent manner, with a maximum up-regulation of 64% by 48 h at 20 ng/ml. In contrast, TGF- β1 down-modulated IL-3 and CSF-1 receptor expression by 54 and 55%, respectively, by 24 h. TGF-β1 did not affect G-CSF receptor expression, in agreement with its inability to affect G-CSF-induced proliferation. The CSF receptor modulation induced by TGF-β1 preceded its effects on CSF-stimulated proliferation. The effects of TGF-β on CSF receptor expression were isoform dependent, thus TGF-β3 was a 10-fold more potent inhibitor of both IL-3- induced colony formation and IL-3 receptor expression than TGF-β1, whereas TGF-β1 was a more potent stimulator of GM-CSF-stimulated colonies and GM- CSF receptor expression than TGF-β3. Therefore, the ability of TGF-β to modulate the CSF receptor density/cell and/or the actual number of progenitors expressing CSF receptors directly correlates with the multifunctional effects of TGF-β in hematopoiesis.