A Phagocytotic Inducer from Herbal Constituent, Pentagalloylglucose Enhances Lipoplex-Mediated Gene Transfection in Dendritic Cells

Kato, Shinichiro; Koizumi, Keiichi; Yamada, Miyuki; Inujima, Akiko; Takeno, Nobuhiro; Nakanishi, Takashi; Sakurai, Hiroaki; Nakagawa, Shinsaku; Saiki, Ikuo

doi:10.1248/bpb.33.1878

Cited by 7 publications

(3 citation statements)

References 59 publications

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“…These results indicate that modifications due to PGG might not directly involve the characteristics of phagocytosis of DC2.4 cells, but may affect the phagosomes or OVA itself, resulting in increased phagocytic activity of DC2.4 cells. We had considered Effect of PGG on antigen presentation that PGG could maintain the phagocytic activity of DC2.4 cells by inhibiting their maturation, because previous reports have shown an inhibitory effect of PGG on nuclear factor (NF)-κB activation, a process considered essential for DC maturation [8][9][10][11]. The present findings also indicate that PGG inhibits maturation of DC2.4 cells, because PGG suppressed cell surface expression of the molecules involved in maturation, namely the MHC class I, MHC class II, and co-stimulatory molecules (CD80, and CD86; Figs 4,5).…”

Section: Discussionmentioning

confidence: 99%

Herbal plant‐derived compound, 1,2,3,4,6‐penta‐O‐galloyl‐β‐d‐glucose, increases cross‐presentation by dendritic cells

Inujima

Yamada

Takeno

et al. 2015

Traditional & Kampo Medicine

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Aim Vaccines have made great contributions to human welfare, and can be used even more effectively with adjuvants. The immune‐inducible effects of adjuvants are classified into four categories: T‐helper (Th)1, Th2, antibody, and cytotoxic T‐lymphocyte (CTL) responses. Exogenous antigens are mainly presented to major histocompatibility complex (MHC) class II molecules, but are also presented to MHC class I molecules via the antigen cross‐presentation process in dendritic cells. The enhancement of cross‐presentation of an injected vaccine antigen by an adjuvant leads to Th1 and CTL responses, resulting in successful intracellular infection and tumor vaccine therapy. Methods It is widely known that herbal medicines have strong immune response effects. With this in mind, we developed a novel vaccine adjuvant from natural compounds used in herbal medicine, through an in vitro model vaccine antigen (ovalbumin, OVA) cross‐presentation assay. Results Among 89 natural compounds, 1,2,3,4,6‐penta‐O‐galloyl‐β‐d‐glucose (PGG) most enhanced cross‐presentation in dendritic cells. While the expression of MHC class II molecules was suppressed, PGG enhanced the expression of MHC class I molecules, restricted to OVA‐derived peptides. Conclusion Restricted MHC class I expression resulting from the use of PGG enhanced cross‐presentation by dendritic cells.

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Section: Discussionmentioning

confidence: 99%

Herbal plant‐derived compound, 1,2,3,4,6‐penta‐O‐galloyl‐β‐d‐glucose, increases cross‐presentation by dendritic cells

Inujima

Yamada

Takeno

et al. 2015

Traditional & Kampo Medicine

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“…It has been reported that PGG can also enhance phagocytosis on dendritic cells; phagocytosis can play a pivotal role in initiating and controlling the T cell-dependent immune response [55]. Hence, it is expected that PGG binding virions can promote influenza virus clearance in vivo .…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Poly-Galloyl-Glucoses Preventing Influenza A Virus Entry into Host Cells

Liu

Xiang

et al. 2014

PLoS ONE

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Hemagglutinin (HA) is essential for Influenza A virus infection, but its diversity of subtypes presents an obstacle to developing broad-spectrum HA inhibitors. In this study, we investigated the molecular mechanisms by which poly-galloyl glucose (pGG) analogs inhibit influenza hemagglutinin (HA) in vitro and in silico. We found that (1) star-shaped pGG analogs exhibit HA-inhibition activity by interacting with the conserved structural elements of the receptor binding domain (RBD); (2) HA inhibition depends on the number of galloyl substituents in a pGG analog; the best number is four; and when PGG binds with two HA trimers at their conserved receptor binding domains (loop 130, loop 220, and 190-α-helix), PGG acts as a molecular glue by aggregating viral particles so as to prevent viral entry into host cells (this was revealed via an in silico simulation on the binding of penta-galloyl-glucose (PGG) with HA). pGGs are also effective on a broad-spectrum influenza A subtypes (including H1, H3, H5, H7); this suggests that pGG analogs can be applied to most influenza A subtypes as a prophylactic against influenza viral infections.

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“…In addition, many researchers have used these cells as DCs in immunological research (Fang et al, 2010;Hayashi et al, 2007;Kato et al, 2010;Okada et al, 2001;Takekoshi et al, 2010). In this study, we evaluated the utility of DC2.4 for a cell-based in vitro assay for skin-sensitization potential.…”

Section: Introductionmentioning

confidence: 99%

Utility of murine dendritic cell line DC2.4 for <i>in vitro </i>assay of skin-sensitization potential

Shiraishi

Ido

Hiromori

et al. 2017

Fundam. Toxicol. Sci.

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-Animal tests, such as the local lymph node assay (LLNA), are the gold standard for assaying skin-sensitizing potential. However, because of concerns about animal welfare, extensive research has been conducted on the use of various cell lines, such as human leukemia cells, for in vitro assays of skin-sensitizing potential, but such assays have not replaced animal tests as stand-alone assays. Because Langerhans cells-a type of dendritic cell-are the main antigen-presenting cells in the epidermis and because they play a central role in the induction of allergic skin disorders, these cells may be useful for skin-sensitizing-potential assays. Here, we investigated the utility of the murine dendritic cell line DC2.4 for in vitro assay of the skin-sensitization potential of 2,4-dinitrochlorobenzene (DNCB), 2-mercaptobenzothiazole (MBT), and α-hexyl cinnamaldehyde (HCA), which are categorized as extremely, moderately, and weakly sensitizing, respectively, on the basis of LLNA results. DC2.4 cell viability decreased dose-dependently with increasing concentration upon treatment with each of the compounds for 24 hr; the DNCB, MBT, and HCA concentrations that resulted in 75% cell viability were 6.07, 120.14, and 118.70 μg/mL, respectively. At nontoxic concentrations (concentrations less than the 75% cell viability concentrations), these compounds dose-dependently upregulated the expression of both CD86 and CD54 on the surface of DC2.4 cells. Their potency decreased in the order DNCB > MBT > HCA, which agrees with the order indicated by the LLNA. These results suggest that DC2.4 cells may be a viable replacement for human leukemia cells in in vitro assays of skin-sensitization potential.

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A Phagocytotic Inducer from Herbal Constituent, Pentagalloylglucose Enhances Lipoplex-Mediated Gene Transfection in Dendritic Cells

Cited by 7 publications

References 59 publications

Herbal plant‐derived compound, 1,2,3,4,6‐penta‐O‐galloyl‐β‐d‐glucose, increases cross‐presentation by dendritic cells

Herbal plant‐derived compound, 1,2,3,4,6‐penta‐O‐galloyl‐β‐d‐glucose, increases cross‐presentation by dendritic cells

The Mechanism of Poly-Galloyl-Glucoses Preventing Influenza A Virus Entry into Host Cells

Utility of murine dendritic cell line DC2.4 for <i>in vitro </i>assay of skin-sensitization potential

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