The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice
The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice
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DOI：
10.1016/s0002-9440(10)63471-2
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发表时间：
2003-09-01
影响因子：
6
通讯作者：
Tipping, PG
中科院分区：
文献类型：
--
作者：
Davenport, P;Tipping, PG
T 细胞和巨噬细胞在动脉粥样硬化斑块中的积累以及针对斑块蛋白的抗体的形成表明适应性免疫有助于动脉粥样硬化的发展。通过将载脂蛋白 E 缺陷 (apoE(-/-)) 小鼠与缺乏驱动 Th1 反应 [白细胞介素 (IL)-12] 或 Th2 反应 (IL-4) 关键细胞因子的小鼠杂交，在小鼠模型中研究了 Th1 和 Th2 辅助细胞亚群对动脉粥样硬化形成的贡献。与apoE-/-小鼠相比，apoE(-/-)/IL-12(-/-)小鼠在30周龄时主动脉根部斑块面积减少了52%（P < 0.001）。 30周龄时，ApoE(-/-)/IL-4(-/-)小鼠斑块面积较apoE(-/-)小鼠减少27%(P < 0.05)，但该阶段斑块明显大于apoE(-/-)/IL-12(-/-)小鼠(P < 0.05)。到 45 周龄时，各品系之间的主动脉根部病变大小没有显着差异，但与 apoE(-/-) (P < 0.05) 和 apoE(-/-)/IL-12(-/-) (P < 0.05) 小鼠相比，apoE(-/-)/IL-4(-/-) 小鼠的主动脉弓疾病减少了 58% 和 64%。与apoE(-/-)/ IL-12(-/-)相比，胸部病变分别减少78%（P < 0.05）。这表明Th1和Th2细胞因子在apoE(-/-)小鼠的各个血管部位的动脉粥样硬化的整个发展过程中发挥作用。
Accumulation of T cells and macrophages in atherosclerotic plaques and the formation of antibodies directed against plaque proteins suggests that adaptive immunity contributes to the development of atherosclerosis. The contribution of Th1 and Th2 helper cell subsets to atherogenesis was studied in a murine model by interbreeding apolipoprotein E-deficient (apoE(-/-)) mice with mice deficient in key cytokines that drive either Th1 responses [interleukin (IL)-12] or Th2 responses (IL-4). Compared to apoE-/- mice, apoE(-/-)/IL-12(-/-) mice had a 52% reduction in plaque area in the aortic root at 30 weeks of age (P < 0.001). ApoE(-/-)/IL-4(-/-) mice had a 27% reduction in plaque area compared to apoE(-/-) mice (P < 0.05) at 30 weeks of age, but their plaques were significantly larger than in apoE(-/-)/IL-12(-/-) mice at this stage (P < 0.05). By 45 weeks of age, there were no significant differences in lesion sizes in the aortic root between the strains, however apoE(-/-)/IL-4(-/-) mice showed a 58% and 64% decrease in disease in their aortic arch compared to apoE(-/-) (P < 0.05) and apoE(-/-)/IL-12(-/-) (P < 0.05) mice, respectively, and a 78% decrease in thoracic lesions compared to apoE(-/-)/ IL-12(-/-) (P < 0.05). This suggests that both Th1 and Th2 cytokines play roles throughout the development of atherosclerosis in various vascular sites in apoE(-/-) mice.