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Retinoid X receptor agonists inhibit phorbol-12-myristate-13-acetate (PMA)-induced differentiation of monocytic THP-1 cells into macrophages

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Abstract

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-α (TNF-α), 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-α 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.

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Acknowledgments

This study was supported by Grant 30670880 and 30600242 from the National Natural Science Foundation, Grant 08ZR1413500 and 08XD1402600 from the Shanghai Municipal Natural Science Foundation and Grant 07060670075 from Vascular Biology, Vascular Benefit Foundation.

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Authors and Affiliations

  1. Department of Cardiology, Renji Hospital, Medical College of Shanghai Jiaotong University, Shanghai, 200127, People’s Republic of China

    Lei Zhou, Ling-hong Shen, Liu-hua Hu, Heng Ge, Jun Pu, Qin Shao & Ben He

  2. Department of Cardiology, the first affiliated hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China

    Da-jun Chai

  3. Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, 200233, People’s Republic of China

    Li Wang & Jin-zhang Zeng

  4. Institute for Biomedical Research, Xiamen University, Xiamen, China

    Jin-zhang Zeng

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  1. Lei Zhou
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  2. Ling-hong Shen
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  3. Liu-hua Hu
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  4. Heng Ge
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  5. Jun Pu
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  7. Qin Shao
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  8. Li Wang
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  9. Jin-zhang Zeng
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  10. Ben He
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Corresponding author

Correspondence to Ben He.

Additional information

Lei Zhou and Ling-hong Shen contributed equally to this study.

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Zhou, L., Shen, Lh., Hu, Lh. et al. Retinoid X receptor agonists inhibit phorbol-12-myristate-13-acetate (PMA)-induced differentiation of monocytic THP-1 cells into macrophages. Mol Cell Biochem 335, 283–289 (2010). https://doi.org/10.1007/s11010-009-0278-z

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