Cooperative effects of gamma interferon and 1-alpha, 25-dihydroxyvitamin D3 in inducing differentiation of human promyelocytic leukemia (HL-60) cells

J. B. Weinberg, M. A. Misukonis, M. M. Hobbs, M. J. Borowitz

Research output: Contribution to journalArticlepeer-review

Abstract

Various agents induce differentiation of human leukemia cells in vitro. Most of these agents cause myeloid differentiation, but phorbol diesters, 1-alpha, 25-dihydroxyvitamin D3 (1,25[OH2]D3), and certain lymphokines cause differentiation to monocyte-like cells. The purpose of this study was to determine the cooperative effects of 1,25(OH2)D3 and the lymphokine gamma interferon (IFN-γ) on HL-60 cell differentiation. The recombinant human IFN-γ or 1,25(OH2)D3 caused a slight reduction in the proliferation of the HL-60 cells (30%-40% reduction at doses of 100-200 U,/ml [0.25-0.50 nM] IFN-γ, or 5-25 nM 1,25[OH2]D3). HL-60 cells treated with 100 U,/ml IFN-G had an eightfold increase in expression of nonspecific esterase (NSE) and a twofold increase in h2O2 production in response to phorbol myristate acetate (PMA). 1,25(OD2)D3 enhanced NSE expression eight-to 30-fold and H2O2 secretion twofold in response to PMA. There was also enhanced expression of HLA-DR and the receptor for C3bi. The 1,25(OH2)D3- and IFN-γ-differentiating effects appeared to be additive or synergistic. Populations of IFN-γ-treated HL-60 cells (but not the 1,25[OH2]D3-treated cells) had multinucleated giant cells. The polykaryons had NSE activity and had some properties of macrophage polykaryons or osteoclasts. 1,25(HO2)D3 did not augment the IFN-γ-induced polykaryon formation.

Original languageEnglish (US)
Pages (from-to)138-142
Number of pages5
JournalExperimental Hematology
Volume14
Issue number2
StatePublished - Jan 1 1986
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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