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Requirement of Differentiative Signals of Both Interferon- and 1,25-Dihydroxyvitamin D₃ for Induction and Secretion of Interleukin-1 by HL-60 Cells

Departments of Human Oncology and Medical Microbiology, University of Wisconsin, Clinical Cancer Center, Madison, Wisconsin 53792

HL-60, a promyelocytic cell line, was treated with both recombinant interferon-gamma (IFN-) and 1,25-(OH)₂ vitamin D₃ (D3), and the effect on monocyte-specific markers was assessed. IFN- and D3 modulated different stages in the monocytic differentiation with respect to interleukin-1 (IL-1) production and secretion. D3 induced production of an intracellular IL-1 activity that was not secreted after lipopolysaccharide stimulation. IFN- did not induce intracellular IL-1 but differentiated HL-60 cells, which had been treated with D3, so that lipopolysaccharide stimulated IL-1 release. Both D3 and IFN- individually enhanced expression of nonspecific esterase; in combination the two agents potentiated each other. Expression of cell surface Leu-M3 antigen was also enhanced by the combination of these two agents. Thus, IFN- not only potentiated expression of D3-induced markers but also conferred phenotypic properties characteristic of monocytes. IFN- may play a role in the differentiation of bone marrow cells to mature monocytes.

¹ Supported in part by a Triton Biosciences Research Fellowship.

² Shaw Scholar.

³ American Cancer Society Professor of Clinical Oncology. To whom requests for reprints should be addressed, at Department of Human Oncology, K4/410 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792.

Received 6/10/87. Revised 12/15/87. Accepted 12/28/87.