Retinoid X receptor agonists inhibit phorbol-12-myristate-13-acetate (PMA)-induced differentiation of monocytic THP-1 cells into macrophages.
Monocyte/macrophage differentiation is an essential process during atherosclerosis development. The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily, which plays an important regulatory role in many metabolic disorders, including atherosclerosis. The purpose of this study was to investigate the effect of RXR agonist on monocyte/macrophage differentiation in vitro. The THP-1 cell line was differentiated into a macrophage-like phenotype by incubation with phorbol-12-myristate-13-acetate (PMA) in the presence or absence of RXR agonist. The viability of adherent differentiated THP-1 cells was determined by MTT assay. Macrophage surface marker CD11b and CD36 was analyzed by flow cytometry. Phagocytosis was measured by fluorescence-labeled latex beads. The production of Cytokine Tunlornecrosisfactor-alpha (TNF-alpha), Interlaken-12p70 (IL-12p70), and Matrix metalloproteinase-9 (MMP-9), each of which was analyzed by ELISA. In the presence of the RXR agonists 9-cis retinoic acid or SR11237, PMA-induced THP-1 cells became less adherent, showed decreased macrophage-like morphological changes, decreased cell surface antigen CD11b and CD36 expression, and down regulated the phagocytosis of latex beads and the production of TNF-alpha and MMP-9. These data suggest that RXR agonists inhibit PMA-induced THP-1 cell differentiation into macrophage-like cells, which may be helpful in understanding the anti-atherosclerotic effect of RXR and its agonists.
Department of Cardiology, Renji Hospital, Medical College of Shanghai Jiaotong University, Shanghai 200127, People's Republic of China.
Lei
L
Zhou
Ling-Hong
LH
Shen
Liu-Hua
LH
Hu
Heng
H
Ge
Jun
J
Pu
Da-Jun
DJ
Chai
Qin
Q
Shao
Li
L
Wang
Jin-Zhang
JZ
Zeng
Ben
B
He
D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D047488:Retinoid X Receptors; D013755:Tetradecanoylphorbol Acetate