The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism
The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism
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DOI：
10.1002/eji.200425776
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Aizawa, Y
中科院分区：
文献类型：
--
作者：
Elnaggar, R;Hanawa, H;Aizawa, Y
白细胞介素(IL)-13是一种由活化的Th2 T淋巴细胞分泌的多效细胞因子。假设Th1细胞因子加重大鼠实验性自身免疫性心肌炎（EAM）， Th2细胞因子改善大鼠实验性自身免疫性心肌炎（EAM）。在这里，我们研究了IL-13对EAM的影响，使用基于流体动力学的IL-13- ig融合基因的传递，以及其作用的可能机制。免疫大鼠第0天，il -13- ig处理大鼠注射pCAGGS-IL-13-Ig，对照大鼠注射pCAGGS-Ig，第1天或第7天。第17天，IL- 13-Ig基因治疗可有效控制EAM，监测指标包括心重/体重比降低、心肌炎减轻和心钠肽mRNA（作为心力衰竭标志物）减少。根据EAM心脏分离细胞中IL-13受体mRNA的表达，我们提出IL-13- ig的靶细胞是CD11b（+）细胞和非心肌细胞非炎症（NCNI）细胞，如成纤维细胞、平滑肌细胞或内皮细胞。IL-13-Ig抑制EAM心脏培养细胞中前列腺素E合酶、环氧化酶-2、诱导型一氧化氮合酶、IL-1 β和tnf - α基因的表达，同时增强IL-1受体拮抗剂基因的表达。我们得出结论，IL-13-Ig改善了EAM，并假设其有效性可能是由于对CD11b（+）和NCNI细胞中的这些免疫分子的影响。
Interleukin (IL)-13 is a pleiotropic cytokine secreted by activated Th2 T lymphocytes. Th1 cytokines are assumed to exacerbate and Th2 cytokines to ameliorate rat experimental autoimmune myocarditis (EAM). Here, we examined the effect of IL-13 on EAM, using a hydrodynamics-based delivery of an IL-13-Ig fusion gene, as well as the possible mechanism of its effect. Rats were immunized on day 0, and IL-13-Ig-treated rats were injected with pCAGGS-IL-13-Ig, and control rats with pCAGGS-Ig, on day I or 7. On day 17, the IL- 13-Ig gene therapy was effective in controlling EAM as monitored by a decreased heart weight/body weight ratio, by reduced myocarditis and by reduced atrial natriuretic peptide mRNA in the heart, as a heart failure marker. On the basis of IL-13 receptor mRNA expression in separated cells from EAM hearts, we proposed that IL-13-Ig target cells were CD11b(+) cells and non-cardiomyocytic noninflammatory (NCNI) cells, such as fibroblasts, smooth muscle or endothelial cells. IL-13-Ig inhibited expression of the genes for prostaglandin E synthase, cyclooxygenase-2, inducible nitric oxide synthase, IL-1 beta and TNF-alpha in cultivated cells from EAM hearts, while it enhanced expression of the IL-1 receptor antagonist gene. We conclude that IL-13-Ig ameliorates EAM and suppose that its effectiveness may be due to the influence on these immunologic molecules in CD11b(+) and NCNI cells.