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Defined Sensing Mechanisms and Signaling Pathways Contribute to the Global Inflammatory Gene Expression Output Elicited by Ionizing Radiation.
Immunity ( IF 32.4 ) Pub Date : 2017-09-19 , DOI: 10.1016/j.immuni.2017.08.017
Prabhat K Purbey 1 , Philip O Scumpia 2 , Peter J Kim 2 , Ann-Jay Tong 1 , Keisuke S Iwamoto 3 , William H McBride 3 , Stephen T Smale 1
Affiliation  

Environmental insults are often detected by multiple sensors that activate diverse signaling pathways and transcriptional regulators, leading to a tailored transcriptional output. To understand how a tailored response is coordinated, we examined the inflammatory response elicited in mouse macrophages by ionizing radiation (IR). RNA-sequencing studies revealed that most radiation-induced genes were strongly dependent on only one of a small number of sensors and signaling pathways, notably the DNA damage-induced kinase ATM, which regulated many IR-response genes, including interferon response genes, via an atypical IRF1-dependent, STING-independent mechanism. Moreover, small, defined sets of genes activated by p53 and NRF2 accounted for the selective response to radiation in comparison to a microbial inducer of inflammation. Our findings reveal that genes comprising an environmental response are activated by defined sensing mechanisms with a high degree of selectivity, and they identify distinct components of the radiation response that might be susceptible to therapeutic perturbation.



中文翻译:

定义的传感机制和信号通路有助于电离辐射促成的全球炎症基因表达输出。

经常通过激活多种信号通路和转录调节剂的多种传感器检测环境损害,从而产生定制的转录输出。为了了解定制的反应是如何协调的,我们检查了电离辐射(IR)在小鼠巨噬细胞中引起的炎症反应。RNA测序研究表明,大多数辐射诱导的基因强烈依赖于少数传感器和信号传导途径中的一种,特别是DNA损伤诱导的激酶ATM,它可以通过多种途径调节许多IR反应基因,包括干扰素反应基因。一种非典型的IRF1依赖性,STING依赖性机制。而且,与炎症的微生物诱导剂相比,被p53和NRF2激活的小型限定基因组解释了对辐射的选择性反应。

更新日期:2017-09-19
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