Gewählte Publikation:
Sillaber, C; Strobl, H; Bevec, D; Ashman, LK; Butterfield, JH; Lechner, K; Maurer, D; Bettelheim, P; Valent, P.
IL-4 regulates c-kit proto-oncogene product expression in human mast and myeloid progenitor cells.
J Immunol. 1991; 147(12):4224-4228
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
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Strobl Herbert
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- Abstract:
- The c-kit proto-oncogene encodes the receptor for a novel hemopoietic cytokine, termed stem cell factor (SCF) or mast cell growth factor (MGF) according to its stimulating spectrum. The human receptor for SCF/MGF is expressed in a subset of normal bone marrow progenitor cells, in leukemic myeloid cells, and in mast cells. In the present study, the effects of recombinant human growth regulators (IL-1 through -9, granulocyte-macrophage/granulocyte/macrophage-CSF, IFN, and TNF) on c-kit proto-oncogene product expression were analyzed by indirect immunofluorescence, by using the anti-SCF/MGFR mAb YB5.B8, and Northern blot analyses, by using a c-kit oligonucleotide probe. Of all cytokines tested, IL-4 was found to down-regulate expression of YB5.B8 Ag in the human mast cell line HMC-1 (maximum inhibition, 51.05 +/- 16.36% mean fluorescence intensity of control; p less than 0.02), as well as in primary leukemic myeloid cells. IL-4 was also found to down-regulate expression of YB5.B8 Ag in normal enriched bone marrow progenitor cells. The effects of IL-4 on expression of YB8.B8 Ag in myeloid/mast cell progenitors was dose and time dependent (maximum effects observed on days 2 and/or 4, by using 50 U/ml of rIL-4) and could be neutralized by using anti-IL-4 mAb. Moreover, IL-4 was found to down-regulate expression of c-kit mRNA in leukemic myeloid cells as well as in HMC-1 cells. Together, these observations identify IL-4 as a regulator of c-kit proto-oncogene product expression in the human system. The effects of IL-4 on human hemopoietic progenitor cells and mast cells may be mediated in part through regulation of SCF/MGFR expression.
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Antibodies, Monoclonal - immunology
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Hematopoietic Cell Growth Factors - analysis Hematopoietic Cell Growth Factors - immunology
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Hematopoietic Stem Cells - chemistry Hematopoietic Stem Cells - drug effects
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Humans -
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Interleukin-4 - pharmacology
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Leukemia, Myeloid - metabolism
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Mast Cells - chemistry Mast Cells - drug effects
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Recombinant Proteins - pharmacology
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Stem Cell Factor -