Dubois C M, Ruscetti F W, Palaszynski E W, Falk L A, Oppenheim J J, Keller J R
Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21701.
J Exp Med. 1990 Sep 1;172(3):737-44. doi: 10.1084/jem.172.3.737.
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.
转化生长因子β（TGF-β）是淋巴细胞和造血祖细胞生长及功能的有效抑制剂。细胞增殖不仅取决于生长因子的存在，还取决于特定受体信号转导复合物的发育。因此，我们研究了TGF-β的抑制作用是否可通过抑制生长因子受体来介导。TGF-β抑制了几种小鼠淋巴细胞和髓细胞系上白细胞介素1受体（IL-1R）的组成性表达水平，以及白细胞介素3（IL-3）诱导的正常小鼠和人骨髓细胞上的IL-1R表达。此外，用TGF-β处理骨髓祖细胞可同时抑制IL-1促进高增殖潜能（HPP）集落形成的能力，并阻断IL-1诱导的EL-4 6.1细胞产生IL-2。这些发现首次证明，TGF-β对造血细胞和T细胞生长及功能活性的抑制作用与IL-1细胞表面受体表达的降低有关。
