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Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sen...

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Autores principales: Znidar, Katarina, Bosnjak, Masa, Semenova, Nina, Pakhomova, Olga, Heller, Loree, Cemazar, Maja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922346/
https://www.ncbi.nlm.nih.gov/pubmed/29721152
http://dx.doi.org/10.18632/oncotarget.24816
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author Znidar, Katarina
Bosnjak, Masa
Semenova, Nina
Pakhomova, Olga
Heller, Loree
Cemazar, Maja
author_facet Znidar, Katarina
Bosnjak, Masa
Semenova, Nina
Pakhomova, Olga
Heller, Loree
Cemazar, Maja
author_sort Znidar, Katarina
collection PubMed
description Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding protein 1 (DAI/ZBP1), DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 (DDX60) and interferon-inducible protein 204 (p204) mRNAs was observed in both tumor cell lines, but their expression was pulse protocol dependent. A decrease in cell survival was also observed; it was cell type, DNA concentration and pulse protocol dependent. Furthermore, the different protocols of electrotransfer led to different cell death outcomes, necrosis and apoptosis, as indicated by an annexin V and 7AAD assays. The obtained data provide new insights on the presence of cytosolic DNA sensors in tumor cells and the activation of different types of cells death after electrotransfer of pDNA. These observations have important implications on the planning of gene therapy or DNA vaccination protocols.
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spelling pubmed-59223462018-05-02 Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation Znidar, Katarina Bosnjak, Masa Semenova, Nina Pakhomova, Olga Heller, Loree Cemazar, Maja Oncotarget Research Paper: Immunology Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding protein 1 (DAI/ZBP1), DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 (DDX60) and interferon-inducible protein 204 (p204) mRNAs was observed in both tumor cell lines, but their expression was pulse protocol dependent. A decrease in cell survival was also observed; it was cell type, DNA concentration and pulse protocol dependent. Furthermore, the different protocols of electrotransfer led to different cell death outcomes, necrosis and apoptosis, as indicated by an annexin V and 7AAD assays. The obtained data provide new insights on the presence of cytosolic DNA sensors in tumor cells and the activation of different types of cells death after electrotransfer of pDNA. These observations have important implications on the planning of gene therapy or DNA vaccination protocols. Impact Journals LLC 2018-04-10 /pmc/articles/PMC5922346/ /pubmed/29721152 http://dx.doi.org/10.18632/oncotarget.24816 Text en Copyright: © 2018 Znidar et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Immunology
Znidar, Katarina
Bosnjak, Masa
Semenova, Nina
Pakhomova, Olga
Heller, Loree
Cemazar, Maja
Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation
title Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation
title_full Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation
title_fullStr Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation
title_full_unstemmed Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation
title_short Tumor cell death after electrotransfer of plasmid DNA is associated with cytosolic DNA sensor upregulation
title_sort tumor cell death after electrotransfer of plasmid dna is associated with cytosolic dna sensor upregulation
topic Research Paper: Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922346/
https://www.ncbi.nlm.nih.gov/pubmed/29721152
http://dx.doi.org/10.18632/oncotarget.24816
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