Graduate School of Life Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
Radiat Res. 2012 Oct;178(4):313-20. doi: 10.1667/rr2989.1. Epub 2012 Sep 11.
The effect of radiation on the intestine has been studied for more than one hundred years. It remains unclear, however, whether this organ uses specific defensive mechanisms against ionizing radiation. The infection with Pseudomonas aeruginosa (PA14) in Caenorhabditis elegans induces up-regulation of innate immune response genes. Here, we found that exposure to ionizing radiation also induces certain innate immune response genes such as F49F1.6 (termed mul-1), clec-4, clec-67, lys-1 and lys-2 in the intestine. Moreover, pre-treatment with ionizing radiation before seeding on PA14 lawn plate significantly increased survival rate in the nematode. We also studied transcription pathway of the mul-1 in response to ionizing radiation. Induction of mul-1 gene was highly dependent on the ELT-2 transcription factor and p38 MAPK. Moreover, the insulin/IGF-1 signal pathway works to enhance induction of this gene. The mul-1 gene showed a different induction pattern from the DNA damage response gene, ced-13, which implies that the expression of this gene might be triggered as an indirect effect of radiation. Silencing of the mul-1 gene led to growth retardation after treatment with ionizing radiation. We describe the cross-tolerance between the response to radiation exposure and the innate immune system.
辐射对肠道的影响已经研究了一百多年。然而,目前尚不清楚该器官是否使用针对电离辐射的特定防御机制。铜绿假单胞菌(PA14)感染秀丽隐杆线虫会诱导先天免疫反应基因的上调。在这里,我们发现电离辐射暴露也会诱导某些先天免疫反应基因,如 F49F1.6(称为 mul-1)、clec-4、clec-67、lys-1 和 lys-2 在肠道中。此外,在用 PA14 菌苔平板接种前进行电离辐射预处理可显著提高线虫的存活率。我们还研究了电离辐射对 mul-1 转录途径的影响。mul-1 基因的诱导高度依赖于 ELT-2 转录因子和 p38 MAPK。此外,胰岛素/IGF-1 信号通路可增强该基因的诱导。mul-1 基因的诱导模式与 DNA 损伤反应基因 ced-13 不同,这意味着该基因的表达可能是辐射的间接影响触发的。沉默 mul-1 基因后,用电离辐射处理会导致生长迟缓。我们描述了对辐射暴露和先天免疫系统的交叉耐受。