Production of granulocyte colony-stimulating factor by THP-1 cells in response to retinoic acid and phorbol ester is mediated through the autocrine production of interleukin-1.
The human monocytic leukemic cell line, THP-1, which differentiates toward macrophages in response to phorbol 12-myristate 13-acetate (PMA) was investigated for its ability to produce granulocyte colony-stimulating factor (G-CSF). G-CSF protein was neither produced during PMA-induced differentiation nor in response to retinoic acid (RA) alone. However, when combined, PMA and RA synergistically stimulated G-CSF production with optimal effect observed at 10(-7)M for both PMA and RA. The synergistic interaction between PMA and RA on G-CSF production appeared to be mediated primarily through production of interleukin-1 beta (IL-1 beta) since neutralization of IL-1 beta activity inhibited about 80% of G-CSF production. It has been previously reported that IL-1 potently synergizes with RA to stimulate G-CSF production by THP-1 cells pretreated with PMA Using synthetic ligands to RA receptors (RAR) and retinoid X receptors (RXR) that selectively bind and activate RAR-RXR and RXR-RXR dimers respectively, we showed that the ability of RA to synergize with IL-1 was signaled through RAR-RXR heterodimer pathway. Finally, we demonstrated that RA can also enhance IL-1-induced G-CSF production in primary monocytes of human peripheral blood.
Wang
Y
Y
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Ohio 45267, USA.
Zhang
J J
JJ
Dai
W
W
Pike
J W
JW
D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007700:Kinetics; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism* / Q000473:pathology; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate