TRANSFORMING GROWTH-FACTOR-BETA IS A POTENT INHIBITOR OF INTERLEUKIN-1 (IL-1) RECEPTOR EXPRESSION - PROPOSED MECHANISM OF INHIBITION OF IL-1 ACTION

Transforming growth factor β (TGF-β) acts as a potent inhibitor of the growth and functions of lymphoid and hemopoietic progenitor cells. Cell proliferation depends not only on the presence of growth factors, but also on the development of specific receptor-signal transducing complexes. We therefore investigated whether the inhibitory actions ofTGF-β could be mediated by inhibition of growth factor receptors. TGF-β inhibited the constitutive level of interleukin 1 receptor (IIr 1R) expression on several murine lymphoid and myeloid progenitor cell lines, as well as IIAR expression induced by interleukin 3 (IIr3) on normal murine and human bone marrow cells. Furthermore, treatment of bone marrow progenitor cells with TGF-β concomitantly inhibited the ability of IIA to promote high proliferative potential (HPP) colony formation as well as blocked IL1-induced IIr2 production by E14 6.1 cells. These findings provide the first evidence that the inhibitory action of TGF-β on the growth and functional activities of hematopoietic and T cells is associated with a reduction in the cell surface receptor expression for IIrl. © 1990, Rockefeller University Press., All rights reserved.