CpG-Oligodeoxynucleotide Treatment Protects against Ionizing Radiation-Induced Intestine Injury

PLoS One. 2013 Jun 21;8(6):e66586. doi: 10.1371/journal.pone.0066586. Print 2013.

Abstract

Background: the bone marrow and the intestine are the major sites of ionizing radiation (IR)-induced injury. Our previous study demonstrated that CpG-oligodeoxynucleotide (ODN) treatment mitigated IR-induced bone marrow injury, but its effect on the intestine is not known. In this study, we sought to determine if CpG-ODN have protective effect on IR-induced intestine injury, and if so, to determine the mechanism of its effect.

Methods and findings: Mice were treated with CpG-ODN after IR. The body weight and survival were daily monitored for 30 days consecutively after exposure. The number of surviving intestinal crypt was assessed by the microcolony survival assay. The number and the distribution of proliferating cell in crypt were evaluated by TUNEL assay and BrdU assay. The expression of Bcl-2, Bax and caspase-3 in crypt were analyzed by Immunohistochemistry assay. The findings showed that the treatment for irradiated mice with CpG-ODN diminished body weight loss, improved 30 days survival, enhanced intestinal crypts survival and maintained proliferating cell population and regeneration in crypt. The reason might involve that CpG-ODN up-regulated the expression of Bcl-2 protein and down-regulated the expression of Bax protein and caspase-3 protein.

Conclusion: CpG-ODN was effective in protection of IR-induced intestine injury by enhancing intestinal crypts survival and maintaining proliferating cell population and regeneration in crypt. The mechanism might be that CpG-ODN inhibits proliferating cell apoptosis through regulating the expression of apoptosis-related protein, such as Bax, Bcl-2 and caspase-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / biosynthesis
  • Down-Regulation / drug effects
  • Down-Regulation / radiation effects
  • Gamma Rays / adverse effects*
  • Intestinal Diseases* / metabolism
  • Intestinal Diseases* / pathology
  • Intestinal Diseases* / prevention & control
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Radiation Injuries, Experimental* / metabolism
  • Radiation Injuries, Experimental* / pathology
  • Radiation Injuries, Experimental* / prevention & control
  • Up-Regulation / drug effects
  • Up-Regulation / radiation effects
  • bcl-2-Associated X Protein / biosynthesis

Substances

  • Bax protein, mouse
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Bcl2 protein, mouse
  • Casp3 protein, mouse
  • Caspase 3

Grants and funding

This work is supported in part by the National Natural Science Foundation of China (No.31070762) and the National Natural Science Foundation of Shanghai (No. 10ZR1437500). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.