IL-4 regulates c-kit proto-oncogene product expression in human mast and myeloid progenitor cells.
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.
Sillaber
C
C
First Medical Department, University of Vienna, Austria.
Strobl
H
H
Bevec
D
D
Ashman
L K
LK
Butterfield
J H
JH
Lechner
K
K
Maurer
D
D
Bettelheim
P
P
Valent
P
P
D000911:Antibodies, Monoclonal / Q000276:immunology; D016298:Hematopoietic Cell Growth Factors / Q000032:analysis* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000378:metabolism; D008407:Mast Cells / Q000737:chemistry / Q000187:drug effects*; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D000911:Antibodies, Monoclonal; D016298:Hematopoietic Cell Growth Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D015847:Interleukin-4