Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock
Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock
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DOI：
10.4049/jimmunol.174.8.4579
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Klinman, DM
中科院分区：
文献类型：
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作者：
Shirota, H;Gursel, I;Klinman, DM
内毒素性休克是一种由细菌性脂多糖引起的危及生命的疾病。LPS触发急性期、促炎性和Th 1细胞因子的释放，这些细胞因子促进内毒素休克的发展。表达抑制性TTAGGG基序的合成寡脱氧核苷酸（ODN）有效地下调由各种免疫刺激引起的促炎性和Th 1细胞因子的产生。目前的结果表明，抑制性ODN保护小鼠免受LPS诱导的内毒素休克。这种保护作用的基础是抑制性ODN结合并阻止STAT 1和STAT 4磷酸化的能力，从而阻断由LPS诱导的IFN-β和IL-12介导的信号级联。这些结果表明，抑制性ODN可能用于治疗内毒素休克。
Endotoxic shock is a life-threatening condition caused by exposure to bacterial LPS. LPS triggers the release of acute phase, proinflammatory, and Th1 cytokines that facilitate the development of endotoxic shock. Synthetic oligodeoxynucleotides (ODN) expressing suppressive TTAGGG motifs effectively down-regulate the production of proinflammatory and Th1 cytokines elicited by a variety of immune stimuli. The current results demonstrate that suppressive ODN protect mice from LPS-induced endotoxic shock. Underlying this protective effect is the ability of suppressive ODN to bind to and prevent the phosphorylation of STAT1 and STAT4, thereby blocking the signaling cascade mediated by LPS-induced IFN-beta and IL-12. These findings suggest that suppressive ODN might be of use in the treatment of endotoxic shock.