Modulation of gene expression via disruption of NF-κB signaling by a bacterial small molecule
Modulation of gene expression via disruption of NF-κB signaling by a bacterial small molecule
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DOI：
10.1126/science.1156499
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发表时间：
2008-07-11
期刊：
影响因子：
56.9
通讯作者：
Ulevitch, Richard J.
中科院分区：
文献类型：
--
作者：
Kravchenko, Vladimir V.;Kaufmann, Gunnar F.;Ulevitch, Richard J.
通过核转录因子核转录因子-kappaB的激活来控制先天免疫反应对于消除入侵的微生物病原体是必不可少的。我们发现细菌N-(3-氧代-十二酰基)高丝氨酸内酯(C12)选择性地损害激活的哺乳动物细胞中核因子-kappaB功能的调节。其结果是特异性抑制刺激介导的对编码炎症细胞因子和其他免疫调节因子的核因子-kappaB反应基因的诱导。这些发现揭示了一种策略，通过这种策略，产生C12的条件病原体，如铜绿假单胞菌，可以减弱先天性免疫系统，以建立和维持人类的局部持续感染，例如在囊性纤维化患者中。
The control of innate immune responses through activation of the nuclear transcription factor NF-kappa B is essential for the elimination of invading microbial pathogens. We showed that the bacterial N-( 3- oxo- dodecanoyl) homoserine lactone ( C12) selectively impairs the regulation of NF-kappa B functions in activated mammalian cells. The consequence is specific repression of stimulus- mediated induction of NF-kappa B- responsive genes encoding inflammatory cytokines and other immune regulators. These findings uncover a strategy by which C12- producing opportunistic pathogens, such as Pseudomonas aeruginosa, attenuate the innate immune system to establish and maintain local persistent infection in humans, for example, in cystic fibrosis patients.