Differences in expression of transcription factor AP-1 in human promyelocytic HL-60 cells during differentiation towards macrophages versus granulocytes

Abstract

Commitment of HL-60 cells to macrophage or granulocytic differentiation was achieved by incubation with 4 beta-phorbol 12-myristate 13-acetate (PMA) for 30-60 min or with dimethyl sulphoxide (DMSO) for 24 h respectively. The commitment stage towards PMA-induced macrophage differentiation was associated with increases in jun B and c-fos mRNA levels, as well as with an increase in the binding activity of transcription factor AP-1. Nevertheless, gel retardation analysis indicated that the AP-1 activity detected in untreated cells was drastically reduced during the commitment stage of DMSO-induced HL-60 differentiation towards granulocytes. When HL-60 cells were treated with sodium butyrate, which induced monocytic differentiation, a remarkable increase in AP-1 binding activity was detected. Treatment of HL-60 cells with 1 alpha,25-dihydroxyvitamin D3, another monocytic differentiation agent, induced a weak, but appreciable, increase in AP-1 activity. Furthermore, addition of sodium butyrate or 1 alpha,25-dihydroxyvitamin D3 to HL-60 cells induced 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 granulocytic differentiation inducer, no enhanced AP-1 binding activity was observed, and only a weak increase in jun D mRNA level was detected. These data indicate that formation of AP-1 is not required for the induction of HL-60 differentiation towards granulocytes, whereas induction of monocytic differentiation is correlated with an increase in AP-1 activity. The differential expression of AP-1 activity may be critical in the differentiation of HL-60 cells towards monocytic or granulocytic lineages.

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

“…It has been reported that mechanical injury induces the activation of ERK, which transmits signals from the cytosol to the nucleus. Potential nucleus targets of ERK include the transcription factors ELK-1, Egr-1 and c-Fos, which are known to regulate cellular growth, differentiation, and migration [35][36][37][38]. Here we found that treatment of SMCs with berberine reduced the levels of phosphorylated ERK stimulated by injury, in the same concentration range that inhibited DNA synthesis and regrowth.…”

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

“…T cells, AP-1 was predominantly composed of JunD, while in monocytes, AP-1 was composed of Fra-1, Fra-2, JunB, and JunD, and in astrocytes, AP-1 is composed of c-Jun and c-Fos (Mollinedo et al, 1993;Fujii et al, 1995;Iwai et al, 2001;Grant and Wigdahl, unpublished observations). Sp1 has been shown to be a transcriptional activator, while Sp3 has been shown to be a repressor of transcriptional activation (reviewed in Black et al, 2001).…”

A Retinoic Acid Receptor β/γ-Selective Prodrug (tazarotene) Plus a Retinoid X Receptor Ligand Induces Extracellular Signal-Regulated Kinase Activation, Retinoblastoma Hypophosphorylation, G0Arrest, and Cell Differentiation

“…For example, tazarotene and other retinoids can block 12-O-tetradecanoylphorbol-13-acetate-induced AP-1 activation-dependent gene regulation in some cells. In the case of HL-60 cells treated with RA, the inhibition of AP-1 as a component of the machinery that propels the cell cycle and cell differentiation effects of RA has been largely discounted (Mollinedo et al, 1993;Kizaki et al, 1996). RA does not alter AP-1 activation in HL-60 cells (Mollinedo et al, 1993;Matikainen et al, 1994;Davis-Alison et al, 1997), nor does a retinoid that has AP-1 inhibitory activity without activating RAR or RXR transcriptional activity cause differentiation or growth arrest (Kizaki et al, 1996).…”