Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues

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 radi...

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Veröffentlicht in:Cellular physiology and biochemistry 2016-01, Vol.40 (3-4), p.716-726
Hauptverfasser: Chen, Yuanyuan, Xu, Yang, Du, Jicong, Guo, Jiaming, Lei, Xiao, Cui, Jianguo, Liu, Cong, Cheng, Ying, Li, Bailong, Gao, Fu, Ju, Jintao, Cai, Jianming, Yang, Yanyong
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container_issue 3-4
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container_title Cellular physiology and biochemistry
container_volume 40
creator Chen, Yuanyuan
Xu, Yang
Du, Jicong
Guo, Jiaming
Lei, Xiao
Cui, Jianguo
Liu, Cong
Cheng, Ying
Li, Bailong
Gao, Fu
Ju, Jintao
Cai, Jianming
Yang, Yanyong
description 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. Conclusion: 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.
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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. 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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. Conclusion: 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.</abstract><cop>Basel, Switzerland</cop><pub>Cell Physiol Biochem Press GmbH &amp; Co KG</pub><pmid>27898411</pmid><doi>10.1159/000452583</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Antigens, CD34 - metabolism
Apoptosis - drug effects
Apoptosis - radiation effects
Cell Count
Cell Survival - drug effects
Cell Survival - radiation effects
Cells, Cultured
Cytokines - metabolism
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - metabolism
HKMT
Hot Temperature
Inflammation - pathology
Male
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - radiation effects
Mice, Inbred BALB C
Mycobacterium tuberculosis - physiology
NF-kappa B - metabolism
Original Paper
Protein Transport - drug effects
Protein Transport - radiation effects
Radiation Injuries - pathology
Radiation Tolerance - drug effects
Radiation Tolerance - radiation effects
Radiation, Ionizing
Radiation-Protective Agents - pharmacology
Radioprotection
Testis - drug effects
Testis - pathology
Testis - radiation effects
Th1 Cells - drug effects
Th1 Cells - immunology
Th1 Cells - radiation effects
Th2 Cells - drug effects
Th2 Cells - immunology
Th2 Cells - radiation effects
Tissues injury
Toll like receptor 2 (TLR2)
title Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues
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