title: GM-CSF induces expression of gp91phox and stimulates retinoic acid-induced p47phox expression in human myeloblastic leukemia cells.
abstract: All-trans retinoic acid (ATRA) combined with granulocyte macrophage colony-stimulating factor (GM-CSF) synergistically increases superoxide-generating activity in human myeloblastic leukemia ML-1 cells. ATRA is known to increase the expression of some NADPH components; however, little is known about the effect of GM-CSF on the expression of these components. We examined the expression of NADPH oxidase components in ML-1 cells treated with ATRA, GM-CSF, or a combination of ATRA and GM-CSF. Expression of p47phox and gp91phox proteins increased markedly after treatment with both reagents. p47phox expression was increased by ATRA alone, and the expression was increased synergistically by the combination of ATRA with GM-CSF. gp91phox was increased by ATRA or GM-CSF alone. The expression of p47phox and gp91phox mRNA underwent similar changes to those seen in protein level. These results indicate that GM-CSF induces expression of gp91phox and enhances ATRA-induced p47phox expression. We speculate that the remarkable induction of gp91phox and p47phox protein is associated with an increase in superoxide-generating activity due to the synergistic effect of ATRA plus GM-CSF.
authors.affiliation: Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Tokyo, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Shimizu
authors.forename: Reiko
authors.initials: R
authors.lastname: Kodama
authors.forename: Shohko
authors.initials: S
authors.lastname: Tsunawaki
authors.forename: Ken
authors.initials: K
authors.lastname: Takeda
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D008562:Membrane Glycoproteins / Q000235:genetics*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D013481:Superoxides; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1