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Intramuscular gene transfer of interleukin-10 cDNA reduces atherosclerosis in apolipoprotein E-knockout mice

  • Masayuki Namiki
    Affiliations
    Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Seinosuke Kawashima
    Correspondence
    Corresponding author. Tel.: +81-78-382-5841; fax: +81-78-382-5859.
    Affiliations
    Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Tomoya Yamashita
    Affiliations
    Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Masanori Ozaki
    Affiliations
    Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Tsuyoshi Sakoda
    Affiliations
    Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Nobutaka Inoue
    Affiliations
    Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Ken-Ichi Hirata
    Affiliations
    Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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  • Ryuichi Morishita
    Affiliations
    Department of Geriatric Medicine, Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Yasufumi Kaneda
    Affiliations
    Department of Geriatric Medicine, Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Mitsuhiro Yokoyama
    Affiliations
    Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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      Abstract

      Atherosclerosis has a close relationship to inflammation, particularly T helper type 1 lymphocyte (Th1) response. Interleukin-10 (IL-10), is thought to suppress Th1 response. To target therapeutic strategy for atherosclerosis, we tested whether IL-10 gene transfer suppresses atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice. Four-week-old apoE-KO mice were divided into two groups and either murine IL-10 cDNA plasmid or empty control vector was transferred to the femoral muscle with the use of Hemagglutinating virus of Japan (HVJ)-liposome. At 1 week after transfection, high cholesterol diet was started and continued for 8 weeks. After euthanasia, histological studies of atherosclerotic lesions and quantitative RT-PCR for Th1 cytokines (IL-12 and IFN-γ) in spleens were performed. IL-10 cDNA gene transfer to the muscle increased plasma IL-10 levels and depressed expression of Th1 cytokines without changing plasma cholesterol levels. IL-10 gene transfer significantly reduced the atherosclerotic plaque area and the macrophage infiltrated area. IL-12 and IFN-γ mRNA expressions in spleens and plasma IFN-γ levels were decreased by IL-10 gene transfer. Therefore, IL-10 gene transfer changed the Th1 response and suppressed atherosclerotic lesion formation in apoE-KO mice. IL-10 could be a new target as a therapeutic tool for the treatment of atherosclerosis.

      Keywords

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