Transbronchial human interleukin-10 gene transfer reduces acute inflammation associated with allograft rejection and intragraft interleukin-2 and tumor necrosis factor-α gene expression in a rat model of lung transplantation
Transbronchial human interleukin-10 gene transfer reduces acute inflammation associated with allograft rejection and intragraft interleukin-2 and tumor necrosis factor-α gene expression in a rat model of lung transplantation
复制标题
DOI：
10.1016/j.healun.2009.10.002
复制
发表时间：
2010-03-01
影响因子：
8.9
通讯作者：
Kondo, Takashi
中科院分区：
文献类型：
--
作者：
Oishi, Hisashi;Okada, Yoshinori;Kondo, Takashi
背景：表达具有潜在免疫调节能力的基因可以减少同种异体移植排斥反应。本研究观察了体外脂质介导的人白介素10(hIL-10)基因转移对大鼠肺移植模型AR和移植物内细胞因子谱的影响。取供体左肺，经支气管注入编码hIL-10(IL-10组)或大肠杆菌β-半乳糖苷酶(对照组)的质粒，与阳离子脂混合。移植后3d和6d，根据受累程度对AR进行组织学分级(1~4期)，并根据受累程度将炎症分级为0~4级。结果：AR分期(3.1+/-0.4vs3.8+/-0.4)、水肿(2.3+/-0.8vs3.2+/-0.4)、肺泡内出血(0.3+/-0.5vs2.2+/-0.8)、IL-10组第3天IL-2和肿瘤坏死因子-α信使RNA表达水平显著低于对照组。结论：体外脂质介导的经支气管hIL-10基因转移减轻了AR相关的急性炎症反应，其机制可能与肺移植大鼠促炎症细胞因子基因表达水平降低有关。J心肺移植2010；29：360-7(C)2010国际心肺移植学会。版权所有。
BACKGROUND: The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). This study examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on AR and the intragraft cytokine profile in a rat model of lung transplantation.METHODS: Left single lung transplants were performed between a highly histoincompatible combination of inbred rats. The donor left lung was extracted and intrabronchially instilled with a plasmid encoding hIL-10 (IL-10 group) or Escherichia coli beta-galactosidase (control group), mixed with a cationic lipid. At 3 and 6 days after transplantation, the degree of AR was graded histologically (stage 1-4) and several pathologic categories of inflammation were scored on a scale of 0 to 4 according to the percentage of involvement. Intragraft cytokine profile was examined by real-time reverse transcription polymerase chain reaction.RESULTS: The stage of AR (3.1 +/- 0.4 vs 3.8 +/- 0.4) and the pathologic scores for edema (2.3 +/- 0.8 vs 3.2 +/- 0.4), intraalveolar hemorrhage (0.3 +/- 0.5 vs 2.2 +/- 0.8), and necrosis (0.3 +/- 0.5 vs 1.2 +/- 0.4) in the IL-10 group were significantly decreased compared with the control group at Day 6. IL-2 and tumor necrosis factor-alpha messenger RNA expression levels on Day 3 were significantly decreased in the IL-10 group.CONCLUSIONS: Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR, which was related to decreased levels of proinflammatory cytokine gene expression in a rat model of lung transplantation. J Heart Lung Transplant 2010;29:360-7 (C) 2010 International Society for Heart and Lung Transplantation. All rights reserved.