关键词： Inflammatory bowel disease (IBD)   Biodosimetry   Gene expression   Inflammation   Mouse model  

摘要： BackgroundIonizing Radiation (IR) is a known pro-inflammatory agent and in the process of development of biomarkers for radiation biodosimetry, a chronic inflammatory disease condition could act as a confounding factor. Hence, it is important to develop radiation signatures that can distinguish between IR-induced inflammatory responses and pre-existing disease. In this study, we compared the gene expression response of a genetically modified mouse model of inflammatory bowel disease (Il10(-/-)) with that of a normal wild-type mouse to potentially develop transcriptomics-based biodosimetry markers that can predict radiation exposure in individuals regardless of pre-existing inflammatory ***-type (WT) and Il10(-/-) mice were exposed to whole body irradiation of 7Gy X-rays. Gene expression responses were studied using high throughput whole genome microarrays in peripheral blood 24h post-irradiation. Analysis resulted in identification of 1962 and 1844 genes differentially expressed (p<0.001, FDR<10%) after radiation exposure in Il10(-/-) and WT mice respectively. A set of 155 genes was also identified as differentially expressed between WT and Il10(-/-) mice at the baseline pre-irradiation level. Gene ontology analysis revealed that the 155 baseline differentially expressed genes were mainly involved in inflammatory response, glutathione metabolism and collagen deposition. Analysis of radiation responsive genes revealed that innate immune response and p53 signaling processes were strongly associated with up-regulated genes, whereas B-cell development process was found to be significant amongst downregulated genes in the two genotypes. However, specific immune response pathways like MHC based antigen presentation, interferon signaling and hepatic fibrosis were associated with radiation responsive genes in Il10(-/-) mice but not WT mice. Further analysis using the IPA prediction tool revealed significant differences in the predicted activation status of