DIFFERENCES IN EXPRESSION OF TRANSCRIPTION FACTOR AP-1 IN HUMAN PROMYELOCYTIC HL-60 CELLS DURING DIFFERENTIATION TOWARDS MACROPHAGES VERSUSGRANULOCYTES

Commitment of HL-60 cells to macrophage or granulocytic differentiatio n was achieved by incubation with 4beta-phorbol 12-myristate 13-acetat e (PMA) for 30-60 min or with dimethyl sulphoxide (DMSO) for 24 h resp ectively. The commitment stage towards PMA-induced macrophage differen tiation was associated with increases in jun B and c-fos mRNA levels, as well as with an increase in the binding activity of transcription f actor AP-1. Nevertheless, gel retardation analysis indicated that the AP-1 activity detected in untreated cells was drastically reduced duri ng the commitment stage of DMSO-induced HL-60 differentiation towards granulocytes. When HL-60 cells were treated with sodium butyrate, whic h induced monocytic differentiation, a remarkable increase in AP-1 bin ding activity was detected. Treatment of HL-60 cells with 1alpha,25-di hydroxyvitamin D3, another monocytic differentiation agent, induced a weak, but appreciable, increase in AP-1 activity. Furthermore, additio n of sodium butyrate or 1alpha,25-dihydroxyvitamin D. to HL-60 cells i nduced the expression of c-fos, c-jun, jun B and jun D proto-oncogenes .. In contrast, when HL-60 cells were treated with retinoic acid, a gr anulocytic differentiation inducer, no enhanced AP-1 binding activity was observed, and only a weak increase in jun D mRNA level was detecte d. These data indicate that formation of AP-1 is not required for the induction of HL-60 differentiation towards granulocytes, whereas induc tion of monocytic differentiation is correlated with an increase in AP -1 activity. The differential expression of AP-1 activity may be criti cal in the differentiation of HL-60 cells towards monocytic or granulo cytic lineages.