Hypothesis: Ran GTPase-based potential therapeutic interventions against lethal microbial infections.
Hypothesis: Ran GTPase-based potential therapeutic interventions against lethal microbial infections.
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DOI：
10.1100/tsw.2002.148
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发表时间：
2002-03-12
影响因子：
--
通讯作者：
Wong PM
中科院分区：
文献类型：
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作者：
Wong PM
宿主先天免疫反应代表了对包括细菌、病毒和真菌在内的多种微生物感染的重要即时防御。哺乳动物细胞中的许多类型的细胞表面受体特异性地识别特定的微生物群体，并通过多种信号转导途径将应答信号传递到细胞核。这些信号通路必须在某个点合并，并且可能是多余的，因为宿主对许多微生物的先天免疫应答非常相似;其特征在于主要细胞类型-巨噬细胞和树突状细胞产生促炎细胞因子，如TNFα、IL-1和IL-6。由于这些细胞因子极大地影响炎症事件级联的幅度，因此细胞因子组中每种细胞因子的比例和实际量可能是每种类型感染的特征。通过系统性上调或下调这些细胞因子的免疫调节将具有重要的治疗潜力。我们最近发现Ran cDNA的两个等位基因- RanT/n和RanC/d -可能具有这些特征。因此，Ran在治疗感染性休克、致死性炭疽休克或腺病毒诱导的毒性方面的应用可能会在未来开辟许多有趣的可能性。
Host innate immune response represents a vital immediate defense against infections by a diverse group of microorganisms that include bacteria, viruses, and fungi. Many types of cell surface receptors in mammalian cells specifically recognize particular groups of microorganisms and transmit response signals to the nuclei via multiple signal transduction pathways. These signaling pathways must merge at some point and are likely to be redundant, as the host innate immune response to many microorganisms is remarkably similar; it is characterized by the production of proinflammatory cytokines such as TNFα, IL-1, and IL-6 by the principal cell types – macrophages and dendritic cells. Since these cytokines influence greatly the magnitude of the cascade of inflammatory events, the proportion and the actual amount of each among the cytokine group may be a characteristic of each type of infections. Immune modulation by systematically up-regulate or down-modulate these cytokines would conceivably have major therapeutic potential. We have recently shown that two alleles of Ran cDNAs – RanT/n and RanC/d – may possess these characteristics. Thus the applica-tion of Ran to the treatment of septic shock, lethal anthrax shock, or adenovirus-induced toxicities may open up many interesting possibilities in the future.