Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats
Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats
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DOI：
10.4049/jimmunol.177.6.3635
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Aizawa, Yoshifusa
中科院分区：
文献类型：
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作者：
Chang, He;Hanawa, Haruo;Aizawa, Yoshifusa
IL-22是与IL-10具有有限同源性的几种细胞因子之一。然而，IL-22的生物学活性大多是未知的。本研究旨在探讨IL-22对大鼠实验性自身免疫性心肌炎（EAM）的作用，并从一个侧面阐明IL-22的生物学活性。在第0天免疫大鼠;在第1天或第6天，使用基于流体动力学的基因递送，用pCAGGS-IL-22-IG注射IL-22-Ig处理的大鼠，用pCAGGS-IG注射对照大鼠。在免疫后第1天或第6天施用IL-22-IG基因治疗，如通过心脏重量与体重比监测的，对控制EAM有效，并且在第17天处死大鼠的心肌炎区域。对EAM心脏纯化细胞中IL-22相关基因表达的检测表明，IL-22-IG作用靶细胞为非心肌细胞（NC）非炎性细胞，如成纤维细胞、平滑肌细胞和内皮细胞。因此，我们检测了rIL-22或含有IL-22-IG的血清对IL-1刺激的从EAM心脏培养的NC细胞中免疫相关基因表达的影响。结果表明，rIL-22或含IL-22-IG的血清均能显著降低IL-1刺激的NC细胞中PGE合成酶、COX-2、MIP-2、MCP-1、IL-6和中性粒细胞趋化因子-2等免疫分子的表达。EAM被基于流体动力学的递送编码IL-22-IG的质粒DNA所抑制，并且这种有效性的原因可能是IL-22抑制了活化的NC非炎性细胞中PG脱氢酶、IL-6和趋化因子的基因表达。
IL-22 is one of several cytokines with limited homology to IL-10. However, the biological activities of IL-22 are mostly unknown. The purpose of this study was to evaluate the effect of IL-22 on rat experimental autoimmune myocarditis (EAM) and elucidate an aspect of the biological activities of IL-22. Rats were immunized on day 0; IL-22-Ig-treated rats were injected with pCAGGS-IL-22-Ig and control rats with pCAGGS-Ig using hydrodynamics-based gene delivery on day 1 or day 6. IL-22-Ig gene therapy administered on day 1 or day 6 after immunization was effective in controlling EAM as monitored by the heart weight to body weight ratio, and the myocarditis area in rats was sacrificed on day 17. Examination of the expression of IL-22-related genes in purified cells from EAM hearts suggested that IL-22-Ig acting target cells were noncardiomyocytic (NC) noninflammatory cells such as fibroblasts, smooth muscle cells, and endothelial cells. Therefore, we examined the effect of rIL-22 or serum containing IL-22-Ig on the expression of immune-relevant genes in IL-1-stimulated NC cells cultured from EAM hearts. Results showed that the expression of immunologic molecules (PGE synthase, cyclooxygenase-2, MIP-2, MCP-1, IL-6, and cytokine-induced neutrophil chemoattractant-2) in IL-1-stimulated NC cells was significantly decreased by rIL-22 or serum containing IL-22-Ig. EAM was suppressed by hydrodynamic-based delivery of plasmid DNA encoding IL-22-Ig, and the reason for this effectiveness may be that IL-22 suppressed gene expression of PG synthases, IL-6, and chemokines in activated NC noninflammatory cells.