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 beta (TGF-beta) 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 of TGF-beta could be mediated by inhibition of growth factor receptors. TGF-beta inhibited the constitutive level of interleukin 1 receptor (IL-1R) expression on several murine lymphoid and myeloid progenitor cell lines, as well as IL-1R expression induced by interleukin 3 (IL-3) on normal murine and human bone marrow cells. Furthermore, treatment of bone marrow progenitor cells with TGF-beta concomitantly inhibited the ability of IL-1 to promote high proliferative potential (HPP) colony formation as well as blocked IL-1-induced IL-2 production by EL-4 6.1 cells. These findings provide the first evidence that the inhibitory action of TGF-beta on the growth and functional activities of hematopoietic and T cells is associated with a reduction in the cell surface receptor expression for IL-1.
Dubois
C M
CM
Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21701.
Ruscetti
F W
FW
Palaszynski
E W
EW
Falk
L A
LA
Oppenheim
J J
JJ
Keller
J R
JR
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000187:drug effects; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000494:pharmacology*
D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D015291:Transforming Growth Factors