• Title/Summary/Keyword: Dendritic

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Anti-tumor Efficacy of a Hepatocellular Carcinoma Vaccine Based on Dendritic Cells Combined with Tumor-derived Autophagosomes in Murine Models

  • Su, Shu;Zhou, Hao;Xue, Meng;Liu, Jing-Yu;Ding, Lei;Cao, Meng;Zhou, Zhen-Xian;Hu, Hong-Min;Wang, Li-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3109-3116
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    • 2013
  • The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

Dendritic Cell Activation by Glucan Isolated from Umbilicaria Esculenta

  • Kim, Hyung-Sook;Kim, Jee-Youn;Lee, Hong-Kyung;Kim, Moo-Sung;Lee, Sang-Rin;Kang, Jong-Soon;Kim, Hwan-Mook;Lee, Kyung-Ae;Hong, Jin-Tae;Kim, Young-Soo;Han, Sang-Bae
    • IMMUNE NETWORK
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    • v.10 no.6
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    • pp.188-197
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    • 2010
  • Background: Lichen-derived glucans have been known to stimulate the functions of immune cells. However, immunostimulatory activity of glucan obtained from edible lichen, Umbilicaria esculenta, has not been reported. Thus we evaluated the phenotype and functional maturation of dendritic cells (DCs) following treatment of extracted glucan (PUE). Methods: The phenotypic and functional maturation of PUE-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. PUE-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity. Finally we detected the activation of MAPK and NF-${\kappa}B$ by immunoblot. Results: Phenotypic maturation of DCs was shown by the elevated expressions of CD40, CD80, CD86, and MHC class I/II molecules. Functional activation of DCs was proved by increased cytokine production of IL-12, IL-$1{\beta}$, TNF-${\alpha}$, and IFN-${\alpha}/{\beta}$, decreased endocytosis, and enhanced proliferation of allogenic T cells. Polymyxin B, specific inhibitor of lipopolysaccharide (LPS), did not affect PUE activity, which suggested that PUE was free of LPS contamination. As a mechanism of action, PUE increased phosphorylation of ERK, JNK, and p38 MAPKs, and enhanced nuclear translocation of NF-${\kappa}B$ p50/p65 in DCs. Conclusion: These results indicate that PUE induced DC maturation via MAPK and NF-${\kappa}B$ signaling pathways.

Ulmi Cortex Prevents Cisplatin-Induced Apoptosis in Mice (시스플라틴에 의한 세포고사에서 유근피(楡根皮)의 효과)

  • Moon, Mi-Hyun;Jeon, Ji-Young;Lee, Seon-Ah;Shin, Yong-Jeen;Ko, Seok-Jae;Moon, Goo
    • Herbal Formula Science
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    • v.16 no.2
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    • pp.229-241
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    • 2008
  • Objectives : The purpose of this study is to investigate the effect of Ulmi Cortex(UC) on the cisplatin-induced cell death. Materials and Methods : I examined several kinds of cell populations such as $CD4^+$ T cells, $CD8^+$ T cells, macrophages and dendritic cells in spleen. Result : When cisplatin was injected to mice, UC recovered total number of cells in spleen and also the number of T cells, macrophages and dendritic cells. UC also effected the activation of $CD4^+$ and $CD8^+$ T cells such as $CD25^+$, $CD69^+$ cells. To further investigate the effect of UC on the cisplatin-induced cell death, I examined the death of splenocyte and total T cells. UC inhibited cisplatin-induced cell death. Conclusion : Taken together, my results suggest that UC may be a beneficial oriental medicine for side effects during anti-tumor therapy.

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Bacterial strains isolated from Jeotgal (salted seafood) induce maturation and cytokine production in mouse bone marrow-derived dendritic cells (마우스 골수 유래 수지상세포의 성숙과 사이토카인 생산에 대한 젓갈 분리균의 효과 연구)

  • Moon, Sun-Young;Park, Eun-Jin;Joo, Hong-Gu
    • Korean Journal of Veterinary Research
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    • v.54 no.3
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    • pp.139-146
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    • 2014
  • Jeotgal (salted seafood) has been one of major fermented foods in Korea for long time. Although there are many studies about Jeotgal in various aspects of food, its immunological importance on hosts has not been elucidated yet. In this study, we investigated if several bacteria isolated from Jeotgal may modulate the function of dendritic cells (DCs), powerful antigen-presenting cells equipped with special immunological capabilities. 4 Jeotgal bacteria were selected as representatives and used for experiments. To treat viable DCs, those bacteria were killed at $60^{\circ}C$ for 30 min. The viability of DCs treated with Jeotgal bacteria was verified and two isolates significantly induced high production of interleukin-12, a representative cell-mediated cytokine of DCs. Surface activation and maturation markers (MHC class II, CD40, CD86) of DCs were analyzed by flow cytometer. In addition, the treated DCs showed significantly high lymphocyte stimulatory capability compared to control DCs based on allogeneic mixed lymphocyte reactions. These observations suggest that Jeotgal isolates can function as immunostimulating bacteria in hosts, like Lactobacillus. Taken together, these experimental evidences may broaden the use of Jeotgal isolates in immunological fields in addition to as a fermented food.

Deep Seawater Increases Dendritic Branches of Cultured Rat Hippocampal Neurons (해양심층수에 의한 해마신경세포 가지돌기 수의 증가)

  • Lee, Hyun-Sook;Nam, Kyung-Soo;Shon, Yun-Hee;Moon, Il-Soo
    • Journal of Life Science
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    • v.18 no.6
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    • pp.897-901
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    • 2008
  • Deep seawater (DSW; deep ocean water) is pure, rich in inorganic materials which have attracted attention for various applications. In this study we investigated the effects of the DSW upwelled from the East Sea, offshore Yang Yang (Korea) on the morphological differentiation of cultured rat hippocampal neurons, which were grown in the minimal essential medium containing 10% (v/v) fetal bovine serum and 25% (v/v) DSW with various hardness. DSW had no effect on initial morphological differentiation (17 hr post-plating). When observed on DIV3, 7, 14, and 17, low hardness (0 and 200) DSW reduced dendritic branching. However, dendritic branches within $80\;{\mu}m$ diameter from the center of soma nearly doubled in neurons grown in hardness 1,000 DSW-containing media. DSW with hardness 600 was more or less same as control groups. These results indicate that DSW with appropriate hardness ameliorates neuronal health.

Inhibitory Effects of Methanol Extract from Nardostachys chinensis on 27-hydroxycholesterol-induced Differentiation of Monocytic Cells

  • Son, Yonghae;Kim, Hyungwoo;Yang, Beodeul;Kim, Boyoung;Park, Young Chul;Kim, Koanhoi
    • Natural Product Sciences
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    • v.23 no.4
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    • pp.239-246
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    • 2017
  • 27-Hydroxycholesterol (27OHChol) has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined the effect of methanol extract of Nardostachys chinensis (Nard) on 27OHChol-induced differentiation using THP-1, a human monocytic cell line. Treatment of monocytic cells with methanol extract of Nard resulted in decreased transcription and surface expression of CD80, CD83, and CD88 elevated by 27OHChol in a dose-dependent manner. Surface levels of MHC class I and II molecules elevated by 27OHChol were also reduced to basal levels by treatment with the Nard extract. Decreased endocytosis activity caused by 27OHChol was recovered by treatment with the Nard extract. CD197 expression and cell attachment were attenuated by the Nard extract. In addition, levels of transcription and surface expression of CD molecules involved in atherosclerosis, such as CD105, CD137, and CD166 upregulated by 27OHChol were significantly decreased by treatment with methanol extract of Nard. These results indicate that methanol extract of Nard down-regulates 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules associated with atherosclerosis. The current study suggests that biological activity of oxygenated cholesterol derivatives can be inhibited by herbal medication.

The Effect of Current and Preheat Temperature on Structure and Hardness of Stellite 12 Alloy Overlayer by PTA Process (PTA법에 의한 스텔라이트 12 합금 육성층의 조직과 경도에 미치는 전류와 예열온도의 영향)

  • Jung, B.H.;Kim, M.G.;Kim, G.D.;Kim, M.Y.;Lee, S.Y.
    • Journal of the Korean Society for Heat Treatment
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    • v.13 no.4
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    • pp.246-252
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    • 2000
  • Stellite 12 alloy-powder was overlaid on 410 stainless steel valve seat using plasma transferred arc(PTA) process. Variation of characteristic of microstructure and hardness of deposit with current(90~150 A) and preheat temperature(R.T.~$400^{\circ}C$) was investigated. Important conclusion obtained are as follows; All welding conditions used produced a sound deposit layer with no defect in single pass welding. The maximum deposit had 4.0~4.8 mm in thickness and its bead width was increased with increase of current and preheat temperature. The deposit showed hypoeutectic microstruture, which was consisting of primary cobalt dendrite and networked $M_7C_3$ type eutectic carbides. The amount of eutectic carbides was decreased and its dendritic secondary arm spacing was increased with increase of current. Hardness of the deposit was decreased with increase of current. Preheat temperature up to $400^{\circ}C$, however, showed little influence on the hardness and microstructure. The hardness was also influenced by diluted Fe content near the interface in addition to microstructure and dendritic secondary arm spacing. Hot hardness at $500^{\circ}C$ showed higher than 300 HV.

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Signaling Through the Murine T Cell Receptor Induces IL-17 Production in the Absence of Costimulation, IL-23 or Dendritic Cells

  • Liu, Xikui K.;Clements, James L.;Gaffen, Sarah L.
    • Molecules and Cells
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    • v.20 no.3
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    • pp.339-347
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    • 2005
  • IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory cytokines, and emerging evidence indicates that it plays a central role in inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T cells, but relatively little is known about how its expression is regulated. In the present study, we examined the requirements and mechanisms for IL-17 expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced rapidly in primary T cells after stimulation of the T cell receptor (TCR) through CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is different in mice than in humans, because "costimulation" of T cells through CD28 only mildly enhanced IL-17 expression, whereas levels of IL-2 were dramatically enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB and CD40L exerted only very weak enhancing effects on IL-17 production. In agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression. However, IL-17 production can occur autonomously in T cells, as neither dendritic cells nor IL-23 were necessary for promoting short-term production of IL-17. Finally, to begin to characterize the TCR-mediated signaling pathway(s) required for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and MAPK signaling pathways.

Tyrosine Hydroxylase - Immunoreactive Dopaminergic Neurons in the OX Retina (Ox retina내 tyrosine - hydroxylase 면역 반응되는 dopaminergic neuron에 대하여)

  • Kim, In Suk;Kim, Jin Suk;Jeon, Young Kee;Jeon, Chang Jin
    • Journal of Korean Ophthalmic Optics Society
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    • v.5 no.2
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    • pp.15-20
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    • 2000
  • The morphology of dopaminergic neurons in the adult ox retina was studied. The dopaminergic neurons were identified using antibody immunocytochemistry. The great majority of tyrosine hydroxylase - immunoreactive neurons were located at the innermost border of the inner nuclear layer. The processes were monostratified and ran laterally within layer 1 of the inner plexiform layer. The second major population of tyrosine hydroxylase - immunoreactive neurons was displaced amacrine cells. The processes of displaced tyrosine hydroxylase - immunoreactive amacrine cells were also located within layer 1 of the inner plexiform layer. Some processes of a few neurons were located in the outer plexiform layer. A very low density of neurons had additional bands of tyrosine hydroxylase - immunoreactive processes in the middle and deep layers of the inner plexiform layer. The processes of dopaminergic neurons widely extended radially and formed large, moderately branched dendritic fields. These processes occasionally had varicosities but did not have "dendritic rings". These results indicate that dopaminergic cells make up specific neuronal cell types in the ox retina.

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Protective Antitumor Activity through Dendritic Cell Immunization is Mediated by NK Cell as Well as CTL Activation

  • Kim, Kwang-Dong;Kim, Jin-Koo;Kim, Se-Jin;Choe, In-Seong;Chung, Tae-Hwa;Choe, Yong-Kyung;Lim, Jong-Seok
    • Archives of Pharmacal Research
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    • v.22 no.4
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    • pp.340-347
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    • 1999
  • Dendritic cells (DCs) are potent professional antigen-presenting cells (APC) capable of inducing the primary T cell response to antigen. Although tumor cells express target antigens, they are incapable of stimulating a tumor-specific immune response due to a defect in the costimulatory signal that is required for optimal activation of T cells. In this work, we describe a new approach using tumor-DC coculture to improve the antigen presenting capacity of tumor cells which does not require a source of tumor-associated antigen. Immunization of a weakly immunogenic and progressive tumor cocultured with none marrow-derived DCs generated an effective tumor vaccine. Immunization with the cocutured DCs was able to induce complete protectiv immunity against tumor challenges and was effective for the induction of tumor-specific CTL (cytotoxic T lymphocyte) activity. Furthermore, high NK cell activity was observed in mice in which tumors were rejected. In addition, immunization with tumor-pulsed DC s induced delayed tumor growth, but not tumor eradication in tumor-bearing mice. Our results demonstrate that coculture of DCs with tumors generated antitumor immunity due to the NK cell activation as well as tumor-specific T cell. This approach would be used for designing tumor vaccines using DCs when the information about tumor antigens is limited.

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