Effect of ATRA and ATO on the expression of tissue factor in NB4 acute promyelocytic leukemia cells and regulatory function of the inflammatory cytokines TNF and IL-1β
In basal conditions, NB4 and HL-60, two acute promyelocytic leukemia cell lines, express high levels of tumor necrosis factor (TNF-alpha) mRNA, whereas they do not synthesize appreciable amounts of the transcripts coding for interleukin-1 beta (IL-1 beta) or interleukin-8 (IL-8). Upon granulocytic differentiation with all-trans retinoic acid (ATRA) or the combination of ATRA and granulocyte-colony-stimulating factor (G-CSF), significant amounts of IL-1 beta and IL-8 mRNAs accumulated in both cell types. These changes in mRNA levels were parallelled by the increased secretion of the two cytokines. Dexamethasone (DEX) had no effect on the induction of IL-1 beta mRNA, while it enhanced the G-CSF-, ATRA- and (ATRA+G-CSF) dependent secretion of the cytokine. In combination with ATRA and G-CSF, the corticosteroid increased the expression of leukocyte alkaline phosphatase, a late marker of granulocytic differentiation.