Requisite role for interleukin-4 in the acceleration of fatty streaks induced by heat shock protein 65 or Mycobacterium tuberculosis
Requisite role for interleukin-4 in the acceleration of fatty streaks induced by heat shock protein 65 or Mycobacterium tuberculosis
复制标题
DOI：
10.1161/01.res.86.12.1203
复制
发表时间：
2000-06-23
影响因子：
20.1
通讯作者：
Harats, D
中科院分区：
文献类型：
--
作者：
George, J;Shoenfeld, Y;Harats, D
热休克蛋白65（HSP 65）可诱导兔和小鼠产生动脉粥样硬化病变。本研究探讨了白细胞介素4（IL-4）在HSP 65和结核分枝杆菌（MT）诱导的炎性表型模型中的作用，与野生型C57 BL/6小鼠中的病变相比，用WSP 65或MT免疫的IL-4敲除（IL-4 KO）小鼠中的脂肪条纹形成显著减少。然而，当注射对照（不含HSP）佐剂时，野生型和IL-4 KO小鼠之间的病变大小没有明显差异。接下来，我们比较研究了IL-4 KO小鼠和野生型小鼠对HSP 65的体液和细胞免疫应答的程度，因为这些被认为对小鼠动脉粥样硬化有影响。与其野生型同窝出生的小鼠相比，HSP 65免疫的IL-4 KO小鼠中的抗HSP 65抗体水平降低，而在对HSP 65的初级细胞免疫应答方面，组间没有明显差异。除了在敲除小鼠中不存在IL-4之外，在伴刀豆球蛋白A致敏的脾细胞中分泌细胞因子干扰素-γ和IL-10的模式在组间相似。与野生型对照组相比，来自用HSP 65免疫的IL-4 KO小鼠的HSP 65引发的腹股沟淋巴细胞分泌更高水平的干扰素-γ（先前显示在体内是促动脉粥样硬化的）。12-/15-脂氧合酶表达，已知由IL-4调节，并有助于小鼠动脉粥样硬化，在病变中不受所用的免疫方案或IL-4破坏的影响。因此，IL-4可以证明是早期“炎性”动脉粥样硬化病变进展中的主要细胞因子，并可以作为免疫调节的靶点。
Atherosclerotic lesions can be induced in rabbits and mice immunized with heat shock protein 65 (HSP65), In the current study, we investigated the role of interleukin (IL)-4 in the HSP65- and Mycobacterium tuberculosis (MT)-induced models that exhibit an inflammatory phenotype, Fatty streak formation in IL-4-knockout (IL-4 KO) mice immunized with WSP65 or MT was significantly reduced when compared with lesions in wild-type C57BL/6 mice. However, when injected with control (HSP-free) adjuvant, no differences were evident in the lesion size between wild-type and the IL-4 KO mice. Next, we studied comparatively the extent of humoral and cellular immune responses to HSP65 in the IL-4 KO and wild-type mice, as those are thought to be influential in murine atherosclerosis. Anti-HSP65 antibody levels were reduced in the HSP65-immunized IL-4 KO mice as compared with their wild-type littermates, whereas no differences were evident between the groups with respect to the primary cellular immune response to HSP65, Other than the absence of IL-4 in the knockout mice, the pattern of secreting cytokines interferon-gamma and IL-IO in concanavalin A-primed splenocytes was similar between the groups. HSP65-primed inguinal lymphocytes from IL-4 KO mice immunized with HSP65 secreted higher levels of interferon-gamma (previously shown to be proatherogenic in vivo) as compared with their wild-type controls. 12-/15-Lipoxygenase expression, known to be regulated by IL-4 and to contribute to murine atherosclerosis, in the lesions was not influenced by the immunization protocol used or by IL-4 disruption. Thus, IL-4 may prove a principal cytokine in the progression of early "inflammatory" atherosclerotic lesions and may serve as a target for immunomodulation.