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 |
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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. 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.</description><identifier>ISSN: 1015-8987</identifier><identifier>EISSN: 1421-9778</identifier><identifier>DOI: 10.1159/000452583</identifier><identifier>PMID: 27898411</identifier><language>eng</language><publisher>Basel, Switzerland: Cell Physiol Biochem Press GmbH & Co KG</publisher><subject>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)</subject><ispartof>Cellular physiology and biochemistry, 2016-01, Vol.40 (3-4), p.716-726</ispartof><rights>2016 The Author(s) Published by S. Karger AG, Basel</rights><rights>2016 The Author(s) Published by S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-f6d2b1b8761e99cb741dfb9d35ce9572bba01377c8caac7d51227cff403b55413</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,2100,27633,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27898411$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Yuanyuan</creatorcontrib><creatorcontrib>Xu, Yang</creatorcontrib><creatorcontrib>Du, Jicong</creatorcontrib><creatorcontrib>Guo, Jiaming</creatorcontrib><creatorcontrib>Lei, Xiao</creatorcontrib><creatorcontrib>Cui, Jianguo</creatorcontrib><creatorcontrib>Liu, Cong</creatorcontrib><creatorcontrib>Cheng, Ying</creatorcontrib><creatorcontrib>Li, Bailong</creatorcontrib><creatorcontrib>Gao, Fu</creatorcontrib><creatorcontrib>Ju, Jintao</creatorcontrib><creatorcontrib>Cai, Jianming</creatorcontrib><creatorcontrib>Yang, Yanyong</creatorcontrib><title>Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues</title><title>Cellular physiology and biochemistry</title><addtitle>Cell Physiol Biochem</addtitle><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.</description><subject>Animals</subject><subject>Antigens, CD34 - metabolism</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - radiation effects</subject><subject>Cell Count</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - radiation effects</subject><subject>Cells, Cultured</subject><subject>Cytokines - metabolism</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>HKMT</subject><subject>Hot Temperature</subject><subject>Inflammation - pathology</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - radiation effects</subject><subject>Mice, Inbred BALB C</subject><subject>Mycobacterium tuberculosis - physiology</subject><subject>NF-kappa B - metabolism</subject><subject>Original Paper</subject><subject>Protein Transport - drug effects</subject><subject>Protein Transport - radiation effects</subject><subject>Radiation Injuries - pathology</subject><subject>Radiation Tolerance - drug effects</subject><subject>Radiation Tolerance - radiation effects</subject><subject>Radiation, Ionizing</subject><subject>Radiation-Protective Agents - pharmacology</subject><subject>Radioprotection</subject><subject>Testis - drug effects</subject><subject>Testis - pathology</subject><subject>Testis - radiation effects</subject><subject>Th1 Cells - drug effects</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - radiation effects</subject><subject>Th2 Cells - drug effects</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - radiation effects</subject><subject>Tissues injury</subject><subject>Toll like receptor 2 (TLR2)</subject><issn>1015-8987</issn><issn>1421-9778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNptkU1v1DAQhi1ERUvhwB2hSFzgkGI7dmwfISq0ahEILWfLH-PKJRsvdoLUf4_ZLHvqyePRo2c08yL0iuALQrj6gDFmnHLZPUFnhFHSKiHk01pjwluppDhFz0u5x_UrFH2GTqmoXUbIGZp-GB_TLqcZ3Bz_QHMZQq1Kk0JzBWZub-I4gm--PrhkjZshx2XbbBYL2S1jKrE0cWqGZZyXXLEBxrE0ZvLN3ltgKnGv3cRSFigv0EkwY4GXh_cc_fx8uRmu2ttvX66Hj7etYx2f29B7aomVoieglLOCER-s8h13oLig1hpMOiGcdMY44TmhVLgQGO4s54x05-h69fpk7vUux63JDzqZqPeNlO-0yXN0I2hne9r3xvWcYhaYUeA7DL5qbW-CtNX1bnXVK_2uO8x6G4uri5oJ0lI0kfX4TDKBK_p-RV1OpWQIx9EE639R6WNUlX1z0C52C_5I_s-mAm9X4JfJd5CPwPD906rQOx8q9fpR6jDlLxeqpOw</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Chen, Yuanyuan</creator><creator>Xu, Yang</creator><creator>Du, Jicong</creator><creator>Guo, Jiaming</creator><creator>Lei, Xiao</creator><creator>Cui, Jianguo</creator><creator>Liu, Cong</creator><creator>Cheng, Ying</creator><creator>Li, Bailong</creator><creator>Gao, Fu</creator><creator>Ju, Jintao</creator><creator>Cai, Jianming</creator><creator>Yang, Yanyong</creator><general>Cell Physiol Biochem Press GmbH & Co KG</general><scope>M--</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>20160101</creationdate><title>Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-f6d2b1b8761e99cb741dfb9d35ce9572bba01377c8caac7d51227cff403b55413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antigens, CD34 - metabolism</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - radiation effects</topic><topic>Cell Count</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - radiation effects</topic><topic>Cells, Cultured</topic><topic>Cytokines - metabolism</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>HKMT</topic><topic>Hot Temperature</topic><topic>Inflammation - pathology</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - radiation effects</topic><topic>Mice, Inbred BALB C</topic><topic>Mycobacterium tuberculosis - physiology</topic><topic>NF-kappa B - metabolism</topic><topic>Original Paper</topic><topic>Protein Transport - drug effects</topic><topic>Protein Transport - radiation effects</topic><topic>Radiation Injuries - pathology</topic><topic>Radiation Tolerance - drug effects</topic><topic>Radiation Tolerance - radiation effects</topic><topic>Radiation, Ionizing</topic><topic>Radiation-Protective Agents - pharmacology</topic><topic>Radioprotection</topic><topic>Testis - drug effects</topic><topic>Testis - pathology</topic><topic>Testis - radiation effects</topic><topic>Th1 Cells - drug effects</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - radiation effects</topic><topic>Th2 Cells - drug effects</topic><topic>Th2 Cells - immunology</topic><topic>Th2 Cells - radiation effects</topic><topic>Tissues injury</topic><topic>Toll like receptor 2 (TLR2)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yuanyuan</creatorcontrib><creatorcontrib>Xu, Yang</creatorcontrib><creatorcontrib>Du, Jicong</creatorcontrib><creatorcontrib>Guo, Jiaming</creatorcontrib><creatorcontrib>Lei, Xiao</creatorcontrib><creatorcontrib>Cui, Jianguo</creatorcontrib><creatorcontrib>Liu, Cong</creatorcontrib><creatorcontrib>Cheng, Ying</creatorcontrib><creatorcontrib>Li, Bailong</creatorcontrib><creatorcontrib>Gao, Fu</creatorcontrib><creatorcontrib>Ju, Jintao</creatorcontrib><creatorcontrib>Cai, Jianming</creatorcontrib><creatorcontrib>Yang, Yanyong</creatorcontrib><collection>Karger Open Access Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Directory of Open Access Journals</collection><jtitle>Cellular physiology and biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yuanyuan</au><au>Xu, Yang</au><au>Du, Jicong</au><au>Guo, Jiaming</au><au>Lei, Xiao</au><au>Cui, Jianguo</au><au>Liu, Cong</au><au>Cheng, Ying</au><au>Li, Bailong</au><au>Gao, Fu</au><au>Ju, Jintao</au><au>Cai, Jianming</au><au>Yang, Yanyong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues</atitle><jtitle>Cellular physiology and biochemistry</jtitle><addtitle>Cell Physiol Biochem</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>40</volume><issue>3-4</issue><spage>716</spage><epage>726</epage><pages>716-726</pages><issn>1015-8987</issn><eissn>1421-9778</eissn><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. 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 & 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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