Namiki Masayuki, Kawashima Seinosuke, Yamashita Tomoya, Ozaki Masanori, Sakoda Tsuyoshi, Inoue Nobutaka, Hirata Ken-Ichi, Morishita Ryuichi, Kaneda Yasufumi, Yokoyama Mitsuhiro
Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan.
Atherosclerosis. 2004 Jan;172(1):21-9. doi: 10.1016/j.atherosclerosis.2003.08.032.
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-gamma) 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-gamma mRNA expressions in spleens and plasma IFN-gamma 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.
动脉粥样硬化与炎症密切相关，尤其是1型辅助性T淋巴细胞（Th1）反应。白细胞介素-10（IL-10）被认为可抑制Th1反应。为了确定针对动脉粥样硬化的治疗策略，我们测试了IL-10基因转移是否能抑制载脂蛋白E基因敲除（apoE-KO）小鼠的动脉粥样硬化。将四周龄的apoE-KO小鼠分为两组，使用日本血凝病毒（HVJ）-脂质体将小鼠IL-10 cDNA质粒或空载体对照转入股四头肌。转染后1周，开始给予高胆固醇饮食并持续8周。安乐死后，对动脉粥样硬化病变进行组织学研究，并对脾脏中Th1细胞因子（IL-12和干扰素-γ）进行定量逆转录聚合酶链反应（RT-PCR）。向肌肉中转移IL-10 cDNA基因可提高血浆IL-10水平，并降低Th1细胞因子的表达，而不改变血浆胆固醇水平。IL-10基因转移显著减少了动脉粥样硬化斑块面积和巨噬细胞浸润面积。IL-10基因转移降低了脾脏中IL-12和干扰素-γ mRNA的表达以及血浆干扰素-γ水平。因此，IL-10基因转移改变了Th1反应并抑制了apoE-KO小鼠动脉粥样硬化病变的形成。IL-10可能成为治疗动脉粥样硬化的一种新的治疗靶点。
