• Title/Summary/Keyword: interleukin-12

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Membrane-bound p35 Subunit of IL-12 on Tumor Cells is Functionally Equivalent to Membrane-bound Heterodimeric Single Chain IL-12 for Induction of Anti-tumor Immunity

  • Hyun-Jin Kim;Sang Min Park;Hayyoung Lee;Young Sang Kim
    • IMMUNE NETWORK
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    • v.16 no.5
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    • pp.305-310
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    • 2016
  • In this study, we compared two different tumor cell vaccines for their induction of anti-tumor immunity; one was a tumor cell clone expressing a membrane-bound form of IL-12 p35 subunit (mbIL-12 p35 tumor clone), and the other was a tumor clone expressing heterodimeric IL-12 as a single chain (mb-scIL-12 tumor clone). The stimulatory effect of mb-scIL-12 on the proliferation of ConA-activated splenocytes was higher than that of mbIL-12 p35 in vitro. However, the stimulatory effect of mbIL-12 p35 was equivalent to that of recombinant soluble IL-12 (3 ng/ml). Interestingly, both tumor clones (mbIL-12 p35 and mb-scIL-12) showed similar tumorigenicity and induction of systemic anti-tumor immunity in vivo, suggesting that tumor cell expression of the membrane-bound p35 subunit is sufficient to induce anti-tumor immunity in our tumor vaccine model.

Assessment of Relationship between Wilms' Tumor Gene (WT1) Expression in Peripheral Blood of Acute Leukemia Patients and Serum IL-12 and C3 Levels

  • Rezai, Omran;Khodadadi, Ali;Heike, Yuji;Mostafai, Ali;Gerdabi, Nader Dashti;Rashno, Mohammad;Abdoli, Zahra
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7303-7307
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    • 2015
  • Background: Leukemia is a common cancer among children and adolescents. Wilms' tumor gene (WT1) is highly expressed in patients with acute leukemia. It is found as a tumor associated antigen (TAA) in various types of hematopoietic malignancies and can be employed as a useful marker for targeted immunotherapy and monitoring of minimal residual disease (MRD). In this regard, WT1 is a transcription factor that promotes gene activation or repression depending on cellular and promoter context. The purpose of this study was assessment of WT1 gene expression in patients with acute leukemia, measurement of IL-12 and C3 levels in serum and evaluation of the relationship between them. Materials and Methods: We evaluated the expression of WT1 mRNA using real-time quantitative RT-PCR and serum levels of IL-12 and C3 using ELISA and nephelometry in peripheral blood of 12 newly diagnosed patients with acute leukemia and 12 controls. Results: The results of our study showed that the average wT1 gene expression in patients was 7.7 times higher than in healthy controls (P <0.05). In addition, IL-12 (P = 0.003) and C3 (P <0.0001) were significantly decreased in the test group compared to controls. Conclusions: WT1 expression levels are significantly higher in patients compared with control subjects whereas serum levels of interleukin-12 and C3 are significantly lower in patients. Wt1 expression levels in patients are inversely related with serum levels of IL-12 and C3.

Interleukin-12 as a Therapeutic Target of Th1-mediated Autoimmune Diseases

  • Kim, Tae-Sung
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.82-83
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    • 2003
  • In the past it was thought that autoimmunity is mediated by antibodies and immune complexes. It has now become clear that many diseases, especially tissue specific, are T cell mediated or at least T cell dependent. The pathogenesis of cell-mediated autoimmune diseases, such as multiple sclerosis, uveitis, diabetes, arthritis, and others, is thought to be in a large measure driven by interferon-gamma-producing antigen-specific T cells polarized toward the Th1 phenotype. (omitted)

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The Study on Sarcoma-180 Anticancer Effects of Juglandis Semen Herbal-acupuncture(JsD) (호도약침(胡桃藥鍼)의 Sarcoma-180 항암효과(抗癌效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Kang, Kye-Sung;Kwon, Ki-Rok;Choi, Sung-Mo;Lee, Seon-Goo
    • Journal of Pharmacopuncture
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    • v.5 no.1 s.8
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    • pp.43-52
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    • 2002
  • Objectives: This study was purposed to investigate the sarcoma-180 anticancer effects of Herbal acupuncture with Juglandis Semen(JsD) in mice. Methods: The Juglandis Semen Herbal-acupuncture was injected on Chung-wan(CV12) of mice with S-180 cancer cell line. Results: The results obtained were summarized as follows; 1. Median survival time of S-180 cancer cell treated with Juglandis Semen Herbal-Acupuncture was not significant.(p < 0.05) 2. Natural killer cell activity was insignificant for S-180 cell treated with Juglandis Semen Herbal-Acupuncture Herbal acupuncture. (P < 0.05) 3. Interleukin-2 productivity of S-180 cell treated with Juglandis Semen Herbal-Acupuncture was not significant.(P < 0.05) Conclusions: According to the results, we can conclude Herbal-acupuncture with Juglandis Semen caused no effects in S-180 cancer cell.

Fidelity of Transgene Transmission and Expression in the Transgenic Mice

  • Zheng, Z. Y.;Y. M. Han;Y. K. Kang;K. B. Oh;W. J. Shin;Lee, K. K.
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.89-89
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    • 2002
  • In this study, we examined transmission efficiency and expression level of the transgenes in the transgenic mice. The transgenic lines secreting a considerable amount of human lactoferrin(LF) thrombopoietin(TPO), interleukin-10(IL-10) into their milk were subjected to access the inheritance and maintenance of transgenic phenotype. They were bred through three generations. The transmission frequency for each generations(F9, F10, F11) of 3 lines was 38.03±10.43%(13/35), 48.33±3.76%(19/39) and 31.83±8.88%(9/28) in the LF line, 51.33±18.98%(20/38), 63.70±35.71%(12/20) and 29.57± 15.05%(8/26) in the TPO line, 38.27±17.74%(15/37), 47.47±29.88%(14/28) and 50.87±5.85%(14/28) in the IL-10 line, respectively. (omitted)

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Suppression of Cyclooxygenase-2 Expression of Skin Fibroblasts by Wogonin, a Plant Flavone from Scutellaria Radix

  • Chi, Yeon-Sook;Kim, Hyun-Pyo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.96-96
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    • 2003
  • Previously, wogonin (5,7-dihydroxy-8-methoxyflavone) was found to suppress proinflammatory enzyme expression including cyclooxygenase-2 (COX-2), contributing to in vivo anti-inflammatory activity against skin inflammation. However, the detailed effect on each skin cell type has not been understood. Therefore, present investigation was carried out to find the effect of wogonin on inflammation-associated gene expression from skin fibroblasts in culture using reverse transcriptase-polymerase chain reaction. As a result, it was found that wogonin (10 - 100 ${\mu}$M) clearly down-regulated COX -2 expression from NIH/3T3 cells treated with 12-O-tetradecanoylphorbol 13-acetate, interleukin-1${\beta}$ or tumor necrosis factor-a. But, the expression levels of COX-1, interleukin-1${\beta}$ and fibronectin were not significantly affected. This finding was well correlated with significant reduction of prostaglandin E$_2$(PGE$_2$) production by wogonin. As a comparison, NS-398 (selective cyclooxygenase-2 inhibitor) did not suppress COX -2 expression and other gene levels, while PGE$_2$production was potently reduced at 0.1 - 10 ${\mu}$M. All these results suggest that COX -2 down-regulation of skin fibroblasts may be, at least in part, one of anti-inflammatory mechanisms of wogonin against skin inflammation.

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Quercitrin Gallate Down-regulates Interleukin-6 Expression by Inhibiting Nuclear Factor-kB Activation in Lipopolysaccharide-stimulated Macrophages

  • Min, Kyung-Rak;Kim, Byung-Hak;Chang, Yoon-Sook;Kim, Young-Soo
    • Natural Product Sciences
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    • v.12 no.2
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    • pp.113-117
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    • 2006
  • Quercitrin gallate was previously isolated from Persicaria lapathifolia (Polygonaceae) as an inhibitor of superoxide production. In the present study, quercitrin gallate was found to inhibit interleukin (IL)-6 production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an $IC_{50}$ value of $63\;{\mu}M$. Furthermore, quercitrin gallate attenuated LPS-induced synthesis of IL-6 transcript but also inhibited LPS-induced IL-6 promoter activity, indicating that the compound could down-regulate IL-6 expression at the transcription level. Since nuclear factor (NF)-kB has been shown to play a key role in LPS-inducible IL-6 expression, an effect of quercitrin gallate on LPS-induced NF-kB activation was further analyzed. Quercitrin gallate exhibited a dosedependent inhibitory effect on LPS-induced nuclear translocation of NF-kB without affecting inhibitory kB (IkB) degradation, and subsequently inhibited LPS-induced NF-kB transcriptional activity in macrophages RAW 264.7. Taken together, quercitrin gallate down-regulated LPS-induced IL-6 expression by inhibiting NF-kB activation, which could provide a pharmacological potential of the compound in IL-6-related immune and inflammatory diseases.

Anti-inflammatory Effect of Dactyloquinone B and Cyclospongiaquinone-1 Mixture in RAW264.7 Macrophage and ICR Mice

  • Lee, Dong-Sung;Hwang, In Hyun;Im, Nam-Kyung;Jeong, Gil-Saeng;Na, MinKyun
    • Natural Product Sciences
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    • v.21 no.4
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    • pp.268-272
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    • 2015
  • Sesquiterpene-quinone is a class of secondary metabolites frequently encountered from marine sponge. The present study was designed to examine the anti-inflammatory action of sponge-derived dactyloquinone B (DQB) and cyclospongiaquinone-1 (CSQ1) mixture using lipopolysaccharide (LPS)-induced inflammatory responses. We measured the production of nitric oxide (NO), tumor necrosis factor-alpha ($TNF-{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), and interleukin-6 (IL-6) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 production, which increased by treatment with LPS, were significantly inhibited by DQB and CSQ1 mixture. It also decreased the production of NO production, and iNOS and COX-2 expression. Furthermore, it reduced 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema of ICR mice. These results demonstrate that sesquiterpene-quinone, DQB and CSQ1 mixture, might serve as a chemical pipeline for the development of anti-inflammatory agent.

The Extract of Gleditsiae Spina Inhibits Mast Cell-Mediated Allergic Reactions Through the Inhibition of Histamine Release and Inflammatory Cytokine Production

  • Shin, Tae-Yong
    • Natural Product Sciences
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    • v.16 no.3
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    • pp.185-191
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    • 2010
  • Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In the present study, the effect of water extract of Gleditsiae Spina (WGS) (Leguminosae), on compound 48/80-induced systemic allergic reaction, anti-DNP IgE antibody-induced local allergic reaction, and histamine release from human mast cell line (HMC-1) cells were studied. In addition, the effect of WGS on phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-induced gene expression and secretion of pro-inflammatory cytokines were investigated using HMC-1 cells. WGS was anally administered to mice for high and fast absorption. WGS inhibited compound 48/80-induced systemic allergic reaction. WGS dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis. WGS reduced histamine release from HMC-1 cells. In addition, WGS decreased the gene expression and secretion of pro-inflammatory cytokines in PMA plus A23187-stimulated HMC-1 cells. These findings provide evidence that WGS could be a candidate as an antiallergic agent.

Prosuction of Cytokine and NO by RAW 264.7 Macrophages and PBMC In Vitro Incubation with Flavonoids

  • Lyu, Su-Yun;Park, Won-Bong
    • Archives of Pharmacal Research
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    • v.28 no.5
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    • pp.573-581
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    • 2005
  • Flavonoids, a group of low molecular weight phenylbenzopyrones, have various pharmacological properties including antioxidant activity, anticancer, and immunomodulatory effects. In the present study, lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate/phytohemagglutinin (PMA/PHA) were used as stimulants for RAW 264.7 macrophages and human peripheral blood mononuclear cell (hPBMC), and tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-2 productions were measured. In addition, flavonoids were examined for their effects on LPS-induced NO production in RAW 264.7 macrophages. The results showed that all compounds were not strongly cytotoxic at the tested concentrations on hPBMC and RAW 264.7 macrophages. On immunomodulatory properties, catechin, epigallocatechin (EGC), naringenin, and fisetin repressed NO production and TNF-${\alpha}$ secretion. Furthermore, catechin, epigallocatechin gallate (EGCG), epicatechin (EC), luteolin, chrysin, quercetin, and galangin increased IL-2 secretion while EGC, apigenin, and fisetin inhibited the secretion. These results indicated that flavonoids have the capacity to modulate the immune response and have a potential anti-inflammatory activity. There was no obvious structure-activity relationship regard to the chemical composition of the flavonoids and their cell biological effects.