Expression of granulocyte colony stimulating factor (G-CSF) and granulocyte/macrophage colony stimulating factor (GM-CSF) mRNA upon stimulation with phorbol ester.
Stimulated human peripheral blood mononuclear cells (MNC) have been shown to express both G-CSF and GM-CSF, Furthermore, G-CSF is expressed by monocytes but not lymphocytes, whereas GM-CSF is expressed largely by T lymphocytes and at low levels in monocytes/macrophages, Here we present the effect of TPA (120-O-tetradecanoyl phorbol-13-acetate) on G-CSF and GM-CSF expression in stimulated human MNCs and T lymphocytes. We observed that TPA (30nM) decreased G-CSF mRNA levels in MNCs, while ionomycin increased G-CSF in a dose-dependent manner. TPA and ionomycin individually increased GM-CSF mRNA levels in T-lymphocytes and MNCs. Further, GM-CSF was induced synergistically by TPA plus ionomycin, whereas this combination markedly decreased G-CSF mRNA levels in MNCs. These data suggest at least two signaling pathway by which G-CSF and GM-CSF and GM-CSF mRNA levels are modulated in a mixed population of monocytes and T lymphocytes, namely protein kinase C (PKC) and calcium. These signals seems to act synergistically in lymphocytes to increase GM-CSF, and not G-CSF mRNA levels specifically. It would also appear these signals act on MNCs in an opposing manner to decrease G-CSF mRNA levels, indicating that activation of PKC and the calcium signaling pathway lead to a cell-type specific modulation of individual cytokines and precise regulation of granulocyte production.
Kothari
S S
SS
Hope Heart Institute, Seattle, WA, USA.
Abrahamsen
M S
MS
Cole
T
T
Hammond
W P
WP
D000328:Adult; D002118:Calcium / Q000502:physiology; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004731:Endotoxins; D007476:Ionophores; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D015759:Ionomycin; C044101:endotoxin, Escherichia coli; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium