Effects of dexamethasone on pro-inflammatory cytokine expression, cell growth and maturation during granulocytic differentiation of acute promyelocytic leukemia cells.
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.
Giannì
M
M
Molecular Biology Unit, Istituto di Ricerche Farmacologiche, Mario Negri, Milano, Italy.
Norio
P
P
Terao
M
M
Falanga
A
A
Marchetti
M
M
Rambaldi
A
A
Garattini
E
E
D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D003907:Dexamethasone; D000469:Alkaline Phosphatase