Activation of Toll-like receptors by intestinal microflora reduces radiation-induced DNA damage in mice

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2014-11, Vol.774, p.22-28
• Main Authors: Chen, Hong, Wang, Zhi-Dong, Chen, Mao-Sheng, Zhang, Xue-Qing, Shen, Li-Ping, Zhang, Jian-Xiang, Chen, Ying
• Format: Article
• Language: English
• Subjects: Animals; Bacteria - immunology; Bioassays; Bone Marrow Cells - radiation effects; Chromosome aberration; Chromosome Aberrations - drug effects; Comet Assay - methods; Digestive system; DNA damage; DNA Damage - drug effects; Gene Expression Regulation - drug effects; Intestinal microflora; Intestines - microbiology; Intestines - radiation effects; Irradiation; Leukocytes - radiation effects; Male; Mice; Mice, Inbred C57BL; Microorganisms; Peptides; Radiation; Rodents; TLRs; Toll-Like Receptors - agonists; Toll-Like Receptors - metabolism
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2014.09.001

•We establish commensal bacteria-depleted mice model.•Commensal microflora-depleted mice have serious irradiation-induced DNA damage.•Bacteria-derived products reduce irradiation-induced DNA damage in mice.•Three DNA repair genes respond to bacteria-derived products.•The data explains the function of TLRs activation in irradiation induced DNA damage. 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.