Genetic immune modulation of Ran GTPase against different microbial pathogens
Genetic immune modulation of Ran GTPase against different microbial pathogens
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DOI：
10.2741/1488
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发表时间：
2004-09-01
影响因子：
3.1
通讯作者：
Wong, PMC
中科院分区：
文献类型：
--
作者：
Chung, SW;Huang, XY;Wong, PMC
感染性休克是由多种微生物感染引起的以促炎细胞因子风暴为特征的疾病。典型的促炎细胞因子包括TNF α、IL 1和IL 6。尽管它们中的一种或多种通常在任何给定的微生物感染中表达，但通常是一种细胞因子的升高在给定感染的特定时间成为主导。在这里，我们表明，腺病毒抗原单独管理导致血清IL 6的主要升高，但不是TNF α。内毒素与腺病毒抗原一起给药导致血清IL 6和TNF α升高。在体内表达RanC/d，但不是RanT/n或LacZ到腹腔巨噬细胞迅速下调这些细胞因子的水平在两个实验情况。它还与减少肝脏炎症损伤和增加对感染性休克的抵抗力相关。我们的结论是RanC/d可以应用于下调生产的细胞因子诱导的微生物产品以外的内毒素，并使抵抗感染性休克诱导的一种或多种微生物病原体的小鼠。本研究阐明了使用RanC/d下调和RanT/n上调多种微生物病原体诱导的宿主先天免疫应答的能力。将RanC/d和RanT/n等位基因之一或两者掺入适当的载体中将产生对生物防御和医学上重要的疾病有价值的遗传疫苗，其中宿主免疫系统对入侵因子的负担严重。
Septic shock characterized by pro-inflammatory cytokine storm can be induced by a variety of microbial infections. Typical pro-inflammatory cytokines include TNFalpha, IL1 and IL6. Although one or more of them is often expressed in any given microbial infection, usually it is the elevation of one cytokine that becomes predominant at a particular time in a given infection. Here we showed that administration of adenoviral antigens alone led to a predominant elevation of serum IL6 but not TNFalpha. Administration of endotoxin together with adenoviral antigens led to elevation of both serum IL6 and TNFalpha. In vivo expression of RanC/d, but not RanT/n or LacZ into peritoneal macrophages rapidly down-modulated the levels of these cytokines in both experimental situations. It also correlated with reduced liver inflammatory damage and increased resistance to septic shock. We conclude that RanC/d can be applied to down-modulating production of cytokines induced by microbial products other than endotoxin and to render resistance to mice against septic shock induced by one or more microbial pathogens. The ability of using RanC/d to down-modulate and RanT/n to up regulate host innate immune response induced by multiple microbial pathogens is illustrated in this study. Incorporation of either or both RanC/d and RanT/n alleles into appropriate vectors will produce genetics vaccines valuable for biodefense and medically important illness in which host immune system against invading agents is severely burdened.