Transforming growth factor-beta trans-modulates the expression of colony stimulating factor receptors on murine hematopoietic progenitor cell lines

作者: SE Jacobsen , FW Ruscetti , CM Dubois , J Lee , TC Boone

DOI: 10.1182/BLOOD.V77.8.1706.1706

关键词: Transforming growth factor, beta 3EndocrinologyInternal medicineTransforming growth factorCell biologyReceptor expressionTGF beta receptor 2Growth factor receptor inhibitorReceptorGrowth factor receptorBiologyTransforming growth factor beta

摘要: Transforming growth factor beta (TGF-beta) is a potent and selective inhibitor of early hematopoietic progenitors leukemic cells. The cellular mechanism(s) underlying this antiproliferative effect is, however, currently unknown. In the present study, we demonstrate that TGF-beta inhibits expression granulocyte-macrophage colony stimulating (GM-CSF), interleukin 3 (IL-3), granulocyte-CSF (G-CSF) receptors on murine factor-dependent independent progenitor cell lines without significant change in receptor affinity. A maximum reduction GM-CSF numbers 65% to 77% was observed by 96-hour incubation with TGF-beta. TGF- induced trans-down-modulation prolonged, noncytotoxic but reversible, not due endogenous production GM- CSF. CSF preceded TGF-beta's inhibitory action. addition, ED50 (1 10 pmol/L) for modulatory similar. surface specific, because other proteins (Ly 5 Ly 17) affected treatment, inhibitors (tumor necrosis interferon) did affect expression. These data suggest downregulation cells involves reducing receptors.

参考文章(39)
JR Keller, IK Mcniece, KT Sill, LR Ellingsworth, PJ Quesenberry, GK Sing, FW Ruscetti, Transforming growth factor β directly regulates primitive murine hematopoietic cell proliferation Blood. ,vol. 75, pp. 596- 602 ,(1990) , 10.1182/BLOOD.V75.3.596.596
SC Murthy, PH Sorensen, AL Mui, G Krystal, Interleukin-3 down-regulates its own receptor. Blood. ,vol. 73, pp. 1180- 1187 ,(1989) , 10.1182/BLOOD.V73.5.1180.1180
J. N. Ihle, H. C. Morse, J. Keller, K. L. Holmes, Interleukin 3 Dependent Retrovirus Induced Lymphomas: Loss of the Ability to Terminally Differentiate in Response to Differentiation Factors Current Topics in Microbiology and Immunology. ,vol. 113, pp. 86- 91 ,(1984) , 10.1007/978-3-642-69860-6_16
J Moeller, H Szöts, M Welle, J Van Snick, P Dörmer, L Hültner, Mouse bone marrow-derived IL-3-dependent mast cells and autonomous sublines produce IL-6. Immunology. ,vol. 67, pp. 408- 413 ,(1989)
D.P. Gearing, J.A. King, N.M. Gough, N.A. Nicola, Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. The EMBO Journal. ,vol. 8, pp. 3667- 3676 ,(1989) , 10.1002/J.1460-2075.1989.TB08541.X
S.M. Seyedin, P.R. Segarini, D.M. Rosen, A.Y. Thompson, H. Bentz, J. Graycar, Cartilage-inducing factor-B is a unique protein structurally and functionally related to transforming growth factor-beta. Journal of Biological Chemistry. ,vol. 262, pp. 1946- 1949 ,(1987) , 10.1016/S0021-9258(18)61601-1
D L Urdal, L S Park, D Friend, S Gillis, Characterization of the cell surface receptor for granulocyte-macrophage colony-stimulating factor. Journal of Biological Chemistry. ,vol. 261, pp. 4177- 4183 ,(1986) , 10.1016/S0021-9258(17)35642-9