title: Activation of Toll-like receptors by intestinal microflora reduces radiation-induced DNA damage in mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China. Electronic address: wangzhidong1977@126.com.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Wang
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Mao-Sheng
authors.initials: MS
authors.lastname: Chen
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Shen
authors.affiliation: Department of Developmental Biology, School of Life Sciences, Central South University, 172 Tong Zipo Road, Changsha 410013, China.
authors.forename: Jian-Xiang
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China. Electronic address: yingchen_29@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology*; D001854:Bone Marrow Cells / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000187:drug effects; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007422:Intestines / Q000382:microbiology* / Q000528:radiation effects; D007962:Leukocytes / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism*
chemical_list: D051193:Toll-Like Receptors
keywords: Chromosome aberration; DNA damage; Intestinal microflora; Irradiation; TLRs