• Title/Summary/Keyword: Immuno-modulating

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Identification of Immune Responsive Genes on Benzene, Toluene and o-Xylene in Jurkat Cells Using 35 k Human Oligomicroarray

  • Sarma, Sailendra Nath;Kim, Youn-Jung;Jeon, Hee-Kyung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.2 no.4
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    • pp.229-235
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    • 2006
  • Volatile organic compounds (VOCs) are a major component of urban air pollution. It is documented that low exposure levels of VOCs induce alterations in immune reactivity resulting in a subsequent higher risk for the development of allergic reactivity and asthma. Despite these facts, there are few reports on the affected primary target and the underlying effective causal mechanisms. So in this study, to better understand the risk of BTX (benzene, toluene and o-xylene) which are the major VOCs and to identify novel biomarkers on immune response to these VOCs exposure in human T lymphocytes, we performed the toxicogenomic study by analyzing of gene expression profiles using 35 k human oligo-microarray. BTX generated specific gene expression patterns in Jurkat cell line. By clustering analysis, we identified some genes as potential markers on immuno-modulating effects of BTX. Four genes of these, HLA-DOA, ITGB2, HMGA2 and 5TAT4 were the most significantly affected by BTX exposure. Thus, this study suggests that these differentially expressed immune genes may play an important role in the pathogenesis on BTX exposure and have significant potential as novel biomarkers of exposure, susceptibility and response to BTC.

Convergence of Cancer Metabolism and Immunity: an Overview

  • Van Dang, Chi;Kim, Jung-whan
    • Biomolecules & Therapeutics
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    • v.26 no.1
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    • pp.4-9
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    • 2018
  • Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

Immunomodulating and Anticoagulant Activity of Glycosaminoglycans Derived from Porcine Testis

  • Yoo, Yung-Choon;Kim, Yeong-Shik;Song, Kyung-Sik;Moon, Eun-Ho;Lee, Kyung-Bok
    • Archives of Pharmacal Research
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    • v.25 no.5
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    • pp.669-674
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    • 2002
  • Glycosaminoglycans (GAGs) were isolated from the porcine testis, and their immuno-modulating and anticoagulant activity was investigated. From anion exchange chromatography (Dowex Macropolous Resin) used for further isolation of porcine testis GAGs (PT-GAGs), two fractions (PT-GAG-1.5 and PT-GAG-16) eluted by different salt concentration were obtained. In immunomodulating activity test, PT-GAG-1.5, but not PT-GAG-16, significantly enhanced the growth of murine peritoneal macrophages. In addition, treatment with PT-GAG-1.5 induced the production of cytokines, interleukin-1$\beta$ (IL-1$\beta$), interferon-${\gamma}$ (IFN-${\gamma}$) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$), from murine microphages. Unexpectedly, both of PT-GAGs had no effect on the growth of murine splenocytes. The anticoagulant activity of PT-GAG-1.5 and PT-GAG-16 was examined by activated partial thromboplastin time (aPTT) assay and thrombin time (TT) assay. Both of PT-kGAGs significantly increased the clotting times of aPTT and TT in a dose-dependent manner. The anticoagulant activity of PT-GAG-16 was found to be higher than that of PT-GAG-1.5. These results suggest that PT-GAGs possess biological activities such as immunomodulating activity and anticoagulant activity.

Four-Week Repeated Oral Toxicity Study of AIP1, a Water-soluble Carbohydrate Fraction from Artemisia iwayomogi in Mice

  • Ryu, Sung-Ha;Jo, Hae-Ran;Kim, Ji-Won;Youn, Hyun-Joo;Kim, Kyu-Bong
    • Toxicological Research
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    • v.27 no.4
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    • pp.261-267
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    • 2011
  • Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found in Korea and used as a traditional medicine to treat liver disease. AIP1, a water-soluble carbohydrate fraction from Artemisia iwayomogi, showed anti-tumor and immuno-modulating activities in animal studies. A subacute toxicological evaluation of AIP1 was performed for 4 weeks in ICR mice. After administration of AIP1 (0, 20, 100, 500 mg/kg/day), the clinical signs, mortalities, body weight changes, hematology, blood clinical biochemistry, urinalysis, organ histopathology, organ weights and gross finding were examined. The results showed that there were no significant differences in body weight changes, food intakes, water consumptions, or organ weights among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally treated with AIP1 and the control group, there was no statistical significance in hematological test or serum biochemical values. Histopathological examination showed no abnormal changes in AIP1 groups. These results suggest that no observed adverse effect level (NOAEL) of the oral administration of AIP1 for 4 weeks was considered to be more than 500 mg/kg/day in mice under the condition investigated in current study.

Biological Activity of the Fractions Extracted from Rhodiola dumulosa (홍경천 추출물의 생리활성)

  • Park, Kyung-Uk;Yoon, Jae-Ho;Kim, Jae-Yong;Jeong, Chang-Ho;Park, Chae-Kyu;Song, Won-Seob;Seo, Kwon-Il
    • Food Science and Preservation
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    • v.12 no.5
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    • pp.496-500
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    • 2005
  • To develop functional food material using Rhodiola dumulosa(RD), the biological activities such as antioxidation, antiproliferation in the cancer cells and immuno-activity in macrophage cells were investigated with hexane, ethylacetate, n-butanol, methanol and water fractions of RD 80% methanol extract. Hydrogen-donating activities of hexane, ethyl acetate, n-butanol, methanol and water fraction were 28.30, 53.21, 35.48, 42.64 and 21.14%, respectively, at a concentration of 100 ${\mu}g/mL$, and the activity of ethyl acetate fraction was similar to as that of BHT. After treated for 48 hrs, the ethyl acetate fraction decreased the proliferation of the A549 and SW480 cells in a dose-dependent manner at concentration of 10, 50, and 100 ${\mu}g/mL$, the activities were higher than other fractions. Morphology of cells treated with the ethyl acetate fraction for 48 hr at 100 ${\mu}g/mL$ was distorted with shrank cell mass, and the cell number was lower than that of control cells the macrophage cells treated. The methanol fraction was significantly induced NO production compared with untreated control cells at above 10 ${\mu}g/mL$ concentration. These results indicate that RD would be used the functional food material.

Molecular Discrimination of Cervidae Antlers and Rangifer Antlers

  • Kim, Eun-Jin;Jung, Young-Ja;Kang, Shin-Jung;Chang, Seung-Yup;Huh, Keun;Nam, Doo-Hyun
    • BMB Reports
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    • v.34 no.2
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    • pp.114-117
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    • 2001
  • Cervi Parvum Cornu is widely used as a hemopoietic, tonifying, growth-promoting, cardiotonic, and immuno-modulating agent in Korea. In order to develop the quality control method of Cervi Parvum Cornu by the identification of the biological source or origin, the molecular approach was applied using PCR (polymerase chain reaction) and PCR-RFLF (PCR-restriction fragment length polymorphism) analysis. In the PCR analysis of the mitochondrial 12S rRNA gene and cytochrome b gene regions, no distinctive DNA bands from Cervidae (deer) antlers and Rangifer (reindeer) antlers were observed. However, when the amplified products in the mitochondrial cytochrome b gene region were subjected to restriction digestion with TaqI, Cervidae antlers showed an undigested state of 380 by band, differently from two bands of 230 by and 1S0 by from Rangifer antlers. Based on this finding, the base sequences of amplified PCR products in the range of mitochondria) cytochrome b gene from Cervidae antlers and Rangifer antlers were determined and subjected to restriction analysis by various endonucleases. The results showed that antlers from Rangifer species could be simply discriminated with other antlers from 8 Cervidae species (Chinese deer, Russian deer, Hong Kong deer, New Zealand deer, Kazakhstan deer, elk, red deer and Sika deer) by PCR-RFLP analysis using AtuI, HaeIII, HpaII or Sau3AI(MboI) as well as TaqI in the range of the mitochondrial cytochrome b gene.

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In Vitro Effects of Water and Methanol Extracts of Melittia inouei on Cytokine Production (유리나방 유충 추출물이 비장 세포로부터 Cytokine 분비에 미치는 효과)

  • Lee, Hyun-Ah;Shon, Hye-Jin;Yang, Young-Taek;Kim, Kyu-Don;Park, Hae-Cheol;Hwang, Jae-Sam;Hwang, Suk-Jo;Ahn, Mi-Young
    • Korean Journal of Pharmacognosy
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    • v.37 no.2 s.145
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    • pp.110-115
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    • 2006
  • Melittia inouei (Yuri Nabang) larvae are used as a crude drug in East Asia for treating stomach cancer and inflammation, and currently reared as a pharmaceutical insect in Jejudo, Korea. This study evaluated the immuno-modulating activity of these extracts, by determining the level of, cytokine production from mouse splenocytes stimulated with the extracts. The Melittia inouei larvae extracts did not induce the splenocyte proliferation. On the other hand, they stimulated the splenocytes to produce cytokines such as $TNF-{\alpha}$, whereas they did not stimulate IL10, IL12 or $IFN-{\gamma}$. The aqueous portion of its plant (Tri-chosanthis kirilowii) extract (sap) was found to be a potent inducer of NO production from the CPAE cells. However, it showed weak inhibitory effects on vascular endothelial growth factor (VEGF) production from splenocytes. These data suggests that a Melittia inouei larvae extract immune modulatory activity in cytokine prodcutions such as $TNF-{\alpha}$ and VEGF which might be related its anticancer effect.

The Modulating Effect of β-1, 3/1, 6-glucan Supplementation in the Diet on Performance and Immunological Responses of Broiler Chickens

  • Zhang, Bo;Guo, Yuming;Wang, Zhong
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.2
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    • pp.237-244
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    • 2008
  • The object of this trial was to investigate the effect of dietary ${\beta}$-1,3/1,6-glucan supplementation on the performance and immunological response of broiler chickens. Two hundred and forty 1-day old male broilers ($39{\pm}1g$) were separated into six treatments which were given six different feeds containing 0 (control), 25, 50, 75, 100 and 125 mg/kg dietary ${\beta}$-1,3/1,6-glucan supplementation. On days 21 and 42, body weight gain, feed consumption and feed conversation rate were recorded as measures of growth performance. The levels of key cytokines in the immuno-regulating pathway: interleukin-1 (IL-1), interleukin-2 (IL-2), interferon $\gamma$(IFN-$\gamma$, tumor necrosis factor $\alpha$(TNF-$\alpha$, and the concentrations of signal molecules: peripheral blood plasma globulin, serum Immunoglobulin G (IgG) and intestinal secretary Immunoglobulin A (sIgA), were measured as indices of the immune response to determine suitable levels of dietary ${\beta}$-1,3/1,6-glucan supplementation. The results indicated that performance was elevated quadratically with dietary ${\beta}$-1,3/1,6-glucan supplementation. Maximal growth performance and an enhanced immunological response were obtained at a supplemented level of 50 mg/kg.

Morphological Changes by Submerged Culture Conditions for the Mycelial Optimal Growth of Cordyceps sinensis and Immunological Properties of Hot Water Extract of Mycelium (동충하초 균사체 최적 성장을 위한 심부배양 조건에 따른 형태학적 변화 및 균사체 열수 추출물의 면역학적 특성)

  • Suh, Hyung-Joo;Choi, Jang-Won
    • KSBB Journal
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    • v.25 no.1
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    • pp.47-54
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    • 2010
  • The mycelial dispersed growth of Cordyceps sinensis was optimized in submerged batch culture at initial pH of 5.0, 150 rpm, and $25^{\circ}C$. The morphological data showed much more dispersed growth of C. sinenesis at initial pH of 5.0. Also, projected area, main hyphal length and number of tips for the mycelial growth of initial pH 5.0 were higher than those of other initial pHs. The industrial medium for mycelial production of C. sinensis was determined to be molasses of 100 g and crushed brewery yeast of 10 g per liter as carbon and nitrogen sources, respectively. With these culture conditions, the maximum production of mycelia was approximately 30.0 g per liter by batch culture in 5-liter jar fermenter with no controlled pH. This result suggests that large-scale mycelia production of C. sinensis may be possible in submerged batch culture. The hot water extract of mycelia from C. sinensis was mainly composed of 83.0% carbohydrate, 11.8% protein, 1.9% lipid, and 2.4% ash and there were present glucose, mannose, galactose, and arabinose as molar ratio of 8.79 : 2.59 : 1.34 : 1.0 in the carbohydrate, respectively. In the experiment using spleen cell and macrophage, the extract showed potent mitogenic and immuno-stimulating activities and among various components, an important factor that contribute to the immunological activities was turned out to be carbohydrate moiety.

Immunostimulating Activity of Beta-Glucan Isolated from the Cell Wall of Mutant Saccharomyces cerevisiae, and Its Anti-Tumor Application in Combination with Cisplatin (Saccharomyces cerevisiae 변이주 세포벽 유래의 베타글루칸의 면역활성 및 Cisplatin과의 병용에 의한 항암 상승작용)

  • Kim, Wan-Jae;Yoon, Taek-Joon;Kim, Dong-Woo;Moon, Won-Kook;Lee, Kwang-Ho
    • The Korean Journal of Food And Nutrition
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    • v.23 no.2
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    • pp.141-146
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    • 2010
  • Cisplatin(cis-diamminedichloroplatium) is one of the most effective anti-cancer drugs being clinically used in the treatment of solid tumors. Despite its therapeutic benefits, its use in clinical practice is often limited because of dose related toxicity. It is known that yeast cell wall beta-glucans possess immuno-modulating properties, which allows for their application in antitumor therapy. IS2 is a kind of beta-glucan derived from the cell wall of mutated Saccharomyces cerevisiae, which exhibits anti-cancer activity in vitro and in vivo. The present study explored the possibility of combination therapy of IS2 with cisplatin. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous administration of IS-2 in combination with cisplatin effectively inhibited tumor metastasis compared with cisplatin alone or IS-2 treatment in vivo. IS-2 effectively enhanced Th1 type cytokines including IFN-$\gamma$, IL-2, IL-12 and GM-CSF. Simultaneously, this combined treatment inhibited production of Th2 type cytokines compared with control. These results suggested that IS-2 can be applied in combination therapy with anti-cancer drugs to minimize their side effects.