TY - JOUR
T1 - Indomethacin potentiates the induction of HL60 differentiation to neutrophils, by retinoic acid and granulocyte colony-stimulating factor, and to monocytes, by vitamin D3
AU - Bunce, Christopher M.
AU - French, Philip J.
AU - Durham, Jennifer
AU - Stockley, Robert A.
AU - Michell, Robert H.
AU - Brown, Geoffrey
PY - 1994/1/1
Y1 - 1994/1/1
N2 - We have confirmed previous observations that HL60 cells treated with a combination of 10 nM retinoic acid (RA), and 30 ng/ml granulocyte colony-stimulating factor (G-CSF) differentiate efficiently towards neutrophils, as characterized by their growth arrest and acquisition of phagocytic ability. Such low concentrations of RA alone provoked only a small proportion of HL60 cells to differentiate, and G-CSF alone provoked no differentiation. In the presence of 30 μM indomethacin (an inhibitor of the enzyme cyclooxygenase that catalyses the first step of prostanoid synthesis), the onset of differentiation provoked by RA plus G-CSF was more rapid, but the final proportion of mature cells was unchanged. Indomethacin also potentiated the growth arrest and differentiation of cells in response to 10 nM RA alone. Although the potentiating effect of indomethacin on RA-induced differentiation occurred at several indomethacin and RA concentrations, it was only apparent when the RA concentration used was alone sufficient to induce a small proportion of cells to differentiate. Indomethacin shifted the G-CSF dose-response curve of cells treated with 10 nM RA to lower G-CSF concentrations. 1α,25-dihydroxy vitamin D3 (VitD3) induces HL60 cells to differentiate to monocytes and indomethacin also potentiated the differentiation of HL60 cells in response to low doses of VitD3 5,8,11-eicosatriynoic acid, an inhibitor of 5-lipoxygenase and 12-lipoxygenase, neither potentiated neutrophil differentiation of HL60 cells, nor prevented indomethacin potentiation of the differentiation of RA-primed cells. Treatment of cells with dexamethasone, a steroid whose effects include inhibition of arachidonate mobilization by phospholipase A2, potentiated RA-primed neutrophil differentiation in a manner similar to indomethacin. These observations suggest that an arachidonate metabolite formed downstream of cyclooxygenase suppresses differentiation of HL60 cells both to neutrophils and monocytes, probably by inhibiting some event essential to commitment to differentiation.
AB - We have confirmed previous observations that HL60 cells treated with a combination of 10 nM retinoic acid (RA), and 30 ng/ml granulocyte colony-stimulating factor (G-CSF) differentiate efficiently towards neutrophils, as characterized by their growth arrest and acquisition of phagocytic ability. Such low concentrations of RA alone provoked only a small proportion of HL60 cells to differentiate, and G-CSF alone provoked no differentiation. In the presence of 30 μM indomethacin (an inhibitor of the enzyme cyclooxygenase that catalyses the first step of prostanoid synthesis), the onset of differentiation provoked by RA plus G-CSF was more rapid, but the final proportion of mature cells was unchanged. Indomethacin also potentiated the growth arrest and differentiation of cells in response to 10 nM RA alone. Although the potentiating effect of indomethacin on RA-induced differentiation occurred at several indomethacin and RA concentrations, it was only apparent when the RA concentration used was alone sufficient to induce a small proportion of cells to differentiate. Indomethacin shifted the G-CSF dose-response curve of cells treated with 10 nM RA to lower G-CSF concentrations. 1α,25-dihydroxy vitamin D3 (VitD3) induces HL60 cells to differentiate to monocytes and indomethacin also potentiated the differentiation of HL60 cells in response to low doses of VitD3 5,8,11-eicosatriynoic acid, an inhibitor of 5-lipoxygenase and 12-lipoxygenase, neither potentiated neutrophil differentiation of HL60 cells, nor prevented indomethacin potentiation of the differentiation of RA-primed cells. Treatment of cells with dexamethasone, a steroid whose effects include inhibition of arachidonate mobilization by phospholipase A2, potentiated RA-primed neutrophil differentiation in a manner similar to indomethacin. These observations suggest that an arachidonate metabolite formed downstream of cyclooxygenase suppresses differentiation of HL60 cells both to neutrophils and monocytes, probably by inhibiting some event essential to commitment to differentiation.
UR - http://www.scopus.com/inward/record.url?scp=0028208979&partnerID=8YFLogxK
M3 - Article
C2 - 7512172
AN - SCOPUS:0028208979
SN - 0887-6924
VL - 8
SP - 595
EP - 604
JO - Leukemia
JF - Leukemia
IS - 4
ER -