Nitric oxide modulation of human leukemia cell differentiation and gene expression.
Nitric oxide (NO) functions as an intercellular messenger molecule in such varied contexts as neurotransmission, immune regulation, and the control of vascular tone. We report that NO, delivered as purified gas or released from the pharmacologic NO donors sodium nitroprusside or 6-morpholino-sydnonimine, caused monocytic differentiation of cells of the human myeloid leukemia cell line HL-60 and altered gene expression. The treated cells stopped proliferating, became spread and vacuolated, had increased expression of nonspecific esterase and the monocyte marker CD14, and displayed increased capacity to produce hydrogen peroxide. Furthermore, these treated cells had increased steady-state expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), but decreased expression of mRNA for the proto-oncogenes c-myc and c-myb. The increase in TNF-alpha and IL-1 beta mRNA levels was due (at least in part) to a new transcription of these specific mRNAs. NO elaborated in the bone marrow microenvironment may have a role in normal and malignant hematopoietic cell growth and differentiation.
Magrinat
G
G
Division of Hematology-Oncology, VA Medical Center, Durham, NC.
Mason
S N
SN
Shami
P J
PJ
Weinberg
J B
JB
D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D016259:Genes, myc; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology*; D018950:Lipopolysaccharide Receptors; D009569:Nitric Oxide / Q000494:pharmacology*; D009857:Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006861:Hydrogen Peroxide