Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression of adipose differentiation-related protein in macrophages

Jian Qiu Gu, Shoichiro Ikuyama, Ping Wei, Bin Fan, Jun Ichi Oyama, Toyoshi Inoguchi, Junji Nishimura

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    Adipose differentiation-related protein (ADRP) is highly expressed in macrophages and human atherosclerotic lesions. We demonstrated that Toll-like receptor (TLR) 4-mediated signals, which are involved in atherosclerosis formation, enhanced the expression of ADRP in macrophages. Lipopolysaccharide (LPS) enhanced the ADRP expression in RAW264.7 cells or peritoneal macrophages from wild-type mice, but not in macrophages from TLR4-deficient mice. Actinomycin D almost completely abolished the LPS effect, whereas cycloheximide decreased the expression at 12 h, indicating that the LPS-induced ADRP expression was stimulated at the transcriptional level and was also mediated by new protein synthesis. LPS enhanced the ADRP promoter activity, in part, by stimulating activator protein (AP)-1 binding to the Ets/AP-1 element. In addition, preceding the increase of the ADRP mRNA, LPS induced the expression of interleukin (IL)-6, IL-1α, and interferon-β mRNAs, all of which stimulated the ADRP expression. Antibodies against these cytokines or inhibitors of c-Jun NH2-terminal kinase and nuclear factor (NF)-κB suppressed the ADRP mRNA level. Thus TLR4 signals stimulate the ADRP expression both in direct and indirect manners. Pycnogenol (PYC), an extract of French maritime pine, suppressed the expression of ADRP and the above-mentioned cytokines. PYC suppressed the ADRP promoter activity and enhancer activity of AP-1 and NF-κB, whereas it did not affect the LPS-induced DNA binding of these factors. In conclusion, TLR4-mediated signals stimulate the ADRP expression in macrophages while PYC antagonizes this process. PYC, a widely used dietary supplement, might be useful for prevention of atherosclerosis.

    Original languageEnglish
    Pages (from-to)E1390-E1400
    JournalAmerican Journal of Physiology - Endocrinology and Metabolism
    Volume295
    Issue number6
    DOIs
    Publication statusPublished - Dec 1 2008

    Fingerprint

    Pinus
    Toll-Like Receptor 4
    Macrophages
    Lipopolysaccharides
    Transcription Factor AP-1
    Messenger RNA
    pycnogenols
    Perilipin-2
    Atherosclerosis
    Cytokines
    JNK Mitogen-Activated Protein Kinases
    Peritoneal Macrophages
    Dactinomycin
    Cycloheximide
    Dietary Supplements
    Interleukin-1
    Protein Binding
    Interferons
    Interleukin-6

    All Science Journal Classification (ASJC) codes

    • Endocrinology, Diabetes and Metabolism
    • Physiology
    • Physiology (medical)

    Cite this

    Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression of adipose differentiation-related protein in macrophages. / Gu, Jian Qiu; Ikuyama, Shoichiro; Wei, Ping; Fan, Bin; Oyama, Jun Ichi; Inoguchi, Toyoshi; Nishimura, Junji.

    In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 295, No. 6, 01.12.2008, p. E1390-E1400.

    Research output: Contribution to journalArticle

    Gu, Jian Qiu ; Ikuyama, Shoichiro ; Wei, Ping ; Fan, Bin ; Oyama, Jun Ichi ; Inoguchi, Toyoshi ; Nishimura, Junji. / Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression of adipose differentiation-related protein in macrophages. In: American Journal of Physiology - Endocrinology and Metabolism. 2008 ; Vol. 295, No. 6. pp. E1390-E1400.
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    AU - Wei, Ping

    AU - Fan, Bin

    AU - Oyama, Jun Ichi

    AU - Inoguchi, Toyoshi

    AU - Nishimura, Junji

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    AB - Adipose differentiation-related protein (ADRP) is highly expressed in macrophages and human atherosclerotic lesions. We demonstrated that Toll-like receptor (TLR) 4-mediated signals, which are involved in atherosclerosis formation, enhanced the expression of ADRP in macrophages. Lipopolysaccharide (LPS) enhanced the ADRP expression in RAW264.7 cells or peritoneal macrophages from wild-type mice, but not in macrophages from TLR4-deficient mice. Actinomycin D almost completely abolished the LPS effect, whereas cycloheximide decreased the expression at 12 h, indicating that the LPS-induced ADRP expression was stimulated at the transcriptional level and was also mediated by new protein synthesis. LPS enhanced the ADRP promoter activity, in part, by stimulating activator protein (AP)-1 binding to the Ets/AP-1 element. In addition, preceding the increase of the ADRP mRNA, LPS induced the expression of interleukin (IL)-6, IL-1α, and interferon-β mRNAs, all of which stimulated the ADRP expression. Antibodies against these cytokines or inhibitors of c-Jun NH2-terminal kinase and nuclear factor (NF)-κB suppressed the ADRP mRNA level. Thus TLR4 signals stimulate the ADRP expression both in direct and indirect manners. Pycnogenol (PYC), an extract of French maritime pine, suppressed the expression of ADRP and the above-mentioned cytokines. PYC suppressed the ADRP promoter activity and enhancer activity of AP-1 and NF-κB, whereas it did not affect the LPS-induced DNA binding of these factors. In conclusion, TLR4-mediated signals stimulate the ADRP expression in macrophages while PYC antagonizes this process. PYC, a widely used dietary supplement, might be useful for prevention of atherosclerosis.

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