title: Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues.
abstract: BACKGROUND
  Exposure to ionizing radiation (IR) often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. Novel safe and effective radioprotectant is urgently required. It has been reported toll like receptor 2 (TLR2) plays a critical role in radioresistance. In this study, we demonstrated the protective effects of Heat-Killed Mycobacterium tuberculosis (HKMT), a potent TLR2 agonist, against IR.
  
  
  METHODS
  Cell survival and apoptosis were determined by CCK-8 assay and Annexin V assay, respectively. An immunofluorescence staining assay was used to detect the translocation of nuclear faktor-kappa beta (NF-kB) p65. Tissue damage was evaluated by Haematoxilin-Eosin (HE) staining assay. We also used a flow cytometry assay to measure the number of nucleated cells and CD34+ hemopoietic stem cells in bone marrow. A western blot assay was used to detect the changes of proteins involving TLR signaling pathway.
  
  
  RESULTS
  We found that HKMT increased cell viability and inhibited cell apoptosis after irradiation. HKMT induced NF-kB translocation and activated Erk1/2, p38 signaling pathway. HKMT also protected bone marrow and testis from destruction. Radiation-induced decreases of nucleated cells and CD34+ hemopoietic stem cells in bone marrow were also inhibited by HKMT treatment. We found that radiation caused increase of inflammatory cytokines was also suppressed by HKMT.
  
  
  CONCLUSIONS
  Our data showed that HKMT exhibited radioprotective effects in vivo and in vitro through activating NF-kB and MAPK signaling pathway, suggesting a potential of HKMT as novel radioprotector.
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Jicong
authors.initials: J
authors.lastname: Du
authors.forename: Jiaming
authors.initials: J
authors.lastname: Guo
authors.forename: Xiao
authors.initials: X
authors.lastname: Lei
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cui
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Bailong
authors.initials: B
authors.lastname: Li
authors.forename: Fu
authors.initials: F
authors.lastname: Gao
authors.forename: Jintao
authors.initials: J
authors.lastname: Ju
authors.forename: Jianming
authors.initials: J
authors.lastname: Cai
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D007249:Inflammation / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D011832:Radiation Injuries / Q000473:pathology; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D016328:NF-kappa B; D011837:Radiation-Protective Agents