Evidence map›Paper›PMID 28791533›Full record

ArticlePharmaceutical research2017

Elucidation of the Mechanism of Increased Activity of Immunostimulatory DNA by the Formation of Polypod-like Structure.

Kohta Mohri, Kengo Nagata, Shozo Ohtsuki, Shiori Toyama, Mao Nonomura, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa, Shinji Sakuma

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Article in Pharmaceutical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Kohta MohriLaboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan. kota.mori@riken.jp.
Kengo NagataLaboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan.
Shozo OhtsukiDepartment of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Shiori ToyamaLaboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan.
Mao NonomuraLaboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan.
Yuki TakahashiDepartment of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Yoshinobu TakakuraDepartment of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Makiya NishikawaDepartment of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Shinji SakumaLaboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, 573-0101, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeWe previously demonstrated that the immunostimulatory activity of CpG DNA is increased by the formation of polypod-like structures. The present study was designed to elucidate the mechanism underlying this increase.

methodsTripodna (three pods) and hexapodna (six pods) were prepared. The cellular uptake of Alexa Fluor 488-labeled DNA samples was examined in several cell lines by measuring the MFI of cells. TNF-α release from RAW264.7 cells was measured after addition of polypodna containing CpG motifs. Dissociation of double stranded DNA was evaluated using FRET.

resultsTripodna and hexapodna were efficiently taken up by macrophage-like RAW264.7 cells and dendritic DC2.4 cells, but not by fibroblast or endothelial cell lines. The uptake by RAW264.7 cells was highest for hexapodna, followed by tripodna, dsDNA, and ssDNA. The release of TNF-α from RAW264.7 cells was also highest for hexapodna. The ratio of TNF-α release to cellular uptake was highest for ssDNA, and lowest for dsDNA. Tripodna and hexapodna were more easily dissociated into single strands after cellular uptake than was dsDNA.

conclusionsThe efficient cellular uptake and prompt dissociation into single strands can be directly related to the high immunostimulatory activity of polypod-like structured DNAs containing CpG motifs.

Indexed as

AnimalsCell Culture TechniquesCell LineDNADNA-Binding ProteinsFluorescent DyesHumansImmunizationMiceMolecular StructureNucleic Acid ConformationStructure-Activity RelationshipTumor Necrosis Factor-alphaDNADNA-Binding ProteinsFluorescent DyesTumor Necrosis Factor-alphaCpG motifinnate immunityphosphodiester DNApolypod-like structureself-assembly

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.