Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaline Phosphatase / biosynthesis
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Alkaline Phosphatase / genetics
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Cell Differentiation / drug effects*
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Cell Division / drug effects
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Cytokines / biosynthesis*
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Cytokines / genetics
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Dexamethasone / pharmacology*
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Drug Synergism
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Enzyme Induction / drug effects
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Gene Expression Regulation, Leukemic / drug effects*
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Granulocyte Colony-Stimulating Factor / pharmacology
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Granulocytes*
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Humans
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Interleukin-1 / biosynthesis
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Interleukin-1 / genetics
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Interleukin-8 / biosynthesis
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Interleukin-8 / genetics
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Leukemia, Promyelocytic, Acute / pathology*
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Neoplasm Proteins / biosynthesis*
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Neoplasm Proteins / genetics
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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Tretinoin / pharmacology
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / pathology
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
Substances
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Cytokines
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Interleukin-1
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Interleukin-8
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Tumor Necrosis Factor-alpha
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Granulocyte Colony-Stimulating Factor
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Tretinoin
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Dexamethasone
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Alkaline Phosphatase