IL-4 regulates c-kit proto-oncogene product expression in human mast and myeloid progenitor cells

C. Sillaber, H. Strobl, D. Bevec, L. K. Ashman, J. H. Butterfield, K. Lechner, D. Maurer, P. Bettelheim, P. Valent

Research output: Contribution to journalArticle

115 Scopus citations

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 < 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 YB5.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.

Original languageEnglish (US)
Pages (from-to)4224-4228
Number of pages5
JournalJournal of Immunology
Volume147
Issue number12
StatePublished - Dec 1 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sillaber, C., Strobl, H., Bevec, D., Ashman, L. K., Butterfield, J. H., Lechner, K., Maurer, D., Bettelheim, P., & Valent, P. (1991). IL-4 regulates c-kit proto-oncogene product expression in human mast and myeloid progenitor cells. Journal of Immunology, 147(12), 4224-4228.