Chen Hong, Wang Zhi-Dong, Chen Mao-Sheng, Zhang Xue-Qing, Shen Li-Ping, Zhang Jian-Xiang, Chen Ying
Department of Developmental Biology, School of Life Sciences, Central South University, 172 Tong Zipo Road, Changsha 410013, China; Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
Mutat Res Genet Toxicol Environ Mutagen. 2014 Nov 1;774:22-8. doi: 10.1016/j.mrgentox.2014.09.001. Epub 2014 Sep 16.
Activation of Toll-like receptors (TLRs) signaling by intestinal microflora-derived bacterial products plays a key role in injury defence for the host. We investigated the role of TLRs activated by intestinal microflora in radiation-induced DNA damage in mice. We analyzed DNA damage induced by 2Gy γ-ray radiation in an intestinal commensal bacteria-depleted mouse model (CD group), in which TLRs (TLR2/6, TLR4 and TLR5) ligand levels in serum were reduced. Chromosomal aberrations were measured in bone marrow cells and peripheral blood leukocyte comet assays were performed. DNA damage was increased in the CD group compared with the control group. Treatment of mice with TLR agonists (CBLB502, LPS and lipopeptide) 1h before radiation resulted in a significant decrease in DNA damage. Genes induced by TLR5 activation were analyzed; activation of TLRs regulated the expression of Gadd45b, Sod2, and Rad21, which are involved in DNA damage repair. In summary, our data indicate that TLRs activation by intestinal microflora reduces DNA damage induced by radiation and regulates expression of several DNA repair genes.
肠道微生物衍生的细菌产物激活Toll样受体（TLRs）信号通路在宿主损伤防御中起关键作用。我们研究了肠道微生物激活的TLRs在小鼠辐射诱导的DNA损伤中的作用。我们在肠道共生菌缺失的小鼠模型（CD组）中分析了2Gyγ射线辐射诱导的DNA损伤，该模型血清中TLRs（TLR2/6、TLR4和TLR5）配体水平降低。检测骨髓细胞中的染色体畸变，并进行外周血白细胞彗星试验。与对照组相比，CD组的DNA损伤增加。在辐射前1小时用TLR激动剂（CBLB502、LPS和脂肽）处理小鼠，导致DNA损伤显著减少。分析了由TLR5激活诱导的基因；TLRs的激活调节了参与DNA损伤修复的Gadd45b、Sod2和Rad21的表达。总之，我们的数据表明，肠道微生物激活的TLRs可减少辐射诱导的DNA损伤，并调节几种DNA修复基因的表达。
