TGF-beta is a bidirectional modulator of cytokine receptor expression on murine bone marrow cells. Differential effects of TGF-beta 1 and TGF-beta 3.
Transforming growth factor beta (TGF-beta), an immunomodulator, has inhibitory as well as stimulatory effects on bone marrow cells. In this study, we demonstrate that TGF-beta 1 also is a bidirectional modulator of CSF receptor expression on murine bone marrow cells. TGF-beta 1 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-beta 1 down-modulated IL-3 and CSF-1 receptor expression by 54 and 55%, respectively, by 24 h. TGF-beta 1 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-beta 1 preceded its effects on CSF-stimulated proliferation. The effects of TGF-beta on CSF receptor expression were isoform dependent, thus TGF-beta 3 was a 10-fold more potent inhibitor of both IL-3-induced colony formation and IL-3 receptor expression than TGF-beta 1, whereas TGF-beta 1 was a more potent stimulator of GM-CSF-stimulated colonies and GM-CSF receptor expression than TGF-beta 3. Therefore, the ability of TGF-beta 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-beta in hematopoiesis.
Jacobsen
S E
SE
Laboratory of Leukocyte Biology, National Cancer Institute, Bethesda, MD 20892.
Ruscetti
F W
FW
Roberts
A B
AB
Keller
J R
JR
D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016184:Receptors, Colony-Stimulating Factor; D016212:Transforming Growth Factor beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor