TLR9‐dependent systemic interferon‐β production by intravenous injection of plasmid DNA/cationic liposome complex in mice

Yoshida, Hiroyuki; Nishikawa, Makiya; Yasuda, Sachiyo; Mizuno, Yumiko; Toyota, Hiroyasu; Kiyota, Tsuyoshi; Takahashi, Rei; Takakura, Yoshinobu

doi:10.1002/jgm.1348

Cited by 21 publications

(16 citation statements)

References 40 publications

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“…bacterial CpG motifs) can activate the immune system via the endosomal TLR9. 127,128 The immune stimulation triggers the proliferation of the B cells and natural killer cells and the release of inflammatory cytokines ( e.g. IFN-γ, IFN-α/β, IL-6, IL-12, GM-CSF and TNF-α), which may lead to serious local and systemic inflammatory reactions.…”

Section: Cytokines As Biomarkers Of Immunomodulatory Properties Ofmentioning

confidence: 99%

Cytokines as biomarkers of nanoparticle immunotoxicity

2013

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Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes.

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Section: Cytokines As Biomarkers Of Immunomodulatory Properties Ofmentioning

confidence: 99%

Cytokines as biomarkers of nanoparticle immunotoxicity

2013

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“…This is in stark contrast to subcutaneously injected lipoplex CpG ODNs, where there is a comparative four- to 13-fold decrease in uptake per cell compared with intravenous injection. The effect of the intravenous infusion on immune activation and inflammation is rapid, with elevation of IL-6 and IFN-β within 2 h, and peak numbers of neutrophils and macrophages accumulating within the lung within 30 min, a nonspecific indicator of inflammation [43]. Intravenous administration into recipient mice also induces higher NK cytolytic function and circulating levels of the Th1 cytokines IFN-γ, IL-12, IL-6, monocyte chemoattractant protein-1 (MCP-1) and TNF-α when using lipoplex CpG ODNs versus free drug [44].…”

Section: Systemic Administration Of Tlr Agonistsmentioning

confidence: 99%

The pharmacokinetics of Toll-like receptor agonists and the impact on the immune system

Engel

Holt

2011

Expert Review of Clinical Pharmacology

166

141

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Toll-like receptor (TLR) ligation activates both the innate and adaptive immune systems, and plays an important role in antiviral and anti-tumor immunity. Therefore, a significant amount of effort has been devoted to exploit the therapeutic potential of TLR agonists. Depending on the therapeutic purpose, either as adjuvants to vaccine, chemotherapy or standalone therapy, TLR agonists have been administered via different routes. Both preclinical and clinical studies have suggested that the route of administration has significant effects on pharmacokinetics, and that understanding these effects is critical to the success of TLR agonist drug development. This article will summarize the pharmacokinetics of TLR agonists with different administration routes, with an emphasis on clinical studies of TLR ligands in oncologic applications.

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“…Therefore, the TLR9-mediated response is mainly induced by a limited number of cells. We showed that depletion of phagocytic cells using clodronate liposomes markedly reduced the inflammatory response induced by the intravenous injection of CpG DNA complexed with cationic liposomes (18). This study also demonstrated that splenectomy hardly reduced the response, which suggests that cells outside the spleen are at least involved in the CpG DNA-induced response.…”

Section: Response To Cpg Dinucleotides In Mammalsmentioning

confidence: 57%

Development of safe and effective nonviral gene therapy by eliminating CpG motifs from plasmid DNA vector

Takakura¹

2012

Front Biosci

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Introduction 3. Biological role of CpG motifs in the body 3.1. Response to CpG dinucleotides in mammals 3.2. CpG motifs in epigenetic regulation of gene expression 4. CpG motifs in plasmid DNA vector 4.1. Inflammatory response to plasmid DNA 4.1.1. Inflammatory response to plasmid DNA 4.1.2. Inflammatory response to plasmid DNA delivered by carrier 4.1.3. TLR9-independent recognition and inflammatory response to plasmid DNA 4.2. Effect of CpG motifs in plasmid DNA on transgene expression from the DNA 4.2.1. Relationship between the transgene expression profile from plasmid DNA and the number of CpG motifs 4.2.2. Factors that link CpG motifs with transgene expression 5. Conclusions 6. Acknowledgement 7. References

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TLR9‐dependent systemic interferon‐β production by intravenous injection of plasmid DNA/cationic liposome complex in mice

Abstract: These findings indicate that, in contrast to the production of IL-6 from splenic macrophages, IFN-beta is produced from phagocytic cells other than splenic macrophages after the injection of CpG lipoplex through the TLR9-dependent pathway.

Cited by 21 publications

References 40 publications

Cytokines as biomarkers of nanoparticle immunotoxicity

Cytokines as biomarkers of nanoparticle immunotoxicity

The pharmacokinetics of Toll-like receptor agonists and the impact on the immune system

Development of safe and effective nonviral gene therapy by eliminating CpG motifs from plasmid DNA vector

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