• Title/Summary/Keyword: cell-mediated immune response

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Tumorigenic Effects of Endocrine-Disrupting Chemicals are Alleviated by Licorice (Glycyrrhiza glabra) Root Extract through Suppression of AhR Expression in Mammalian Cells

  • Chu, Xiao Ting;Cruz, Joseph Dela;Hwang, Seong Gu;Hong, Heeok
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5117-5121
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    • 2014
  • Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.

Effect of Butyrate on Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Therapy (Butyrate가 Adenoviral Vector로 이입한 Herpes Simplex Virus Thymidine Kinase 유전자치료에 미치는 영향)

  • Park, Jae-Yong;Kim, Jeong-Ran;Chang, Hee-Jin;Kim, Chang-Ho;Park, Jae-Ho;Jung, Tae-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.3
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    • pp.587-595
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    • 1998
  • Background: Recombinant adenovirus hold promise as vectors to carry therapeutic genes for several reasons: 1) they can infect both dividing and non-dividing cells; 2) they have the ability to directly transduce tissues in vivo; 3) they can easily be produced in high titer; and 4) they have an established record of safety as vaccination material. However, one of the major limitation in the use of adenoviruses is that transgene expression is quite short because adenovirusees insert their DNA genome episomally rather than by chromosomal integration, and an immune response against the virus destroys cells expressing the therapeutic gene. Since sodium butyrate has been reported to induce adenovirus-mediated gene expression, we hypothesized that treatment of tumor cells, transduced with herpes simples virus thymidine kinase(HSVtk) gene using adenoviral vector, with butyrate could augment the effect of gene therapy. Methods: We transduced HSVtk gene, driven by the cytomegalovirus promoter, into REN cell line(human mesothelioma cell line). Before proceeding with the comparison of HSVtk/ganciclovir mediated bystander killing, we evaluated the effect of butyrate on the growth of tumor cells in order to rule out a potential antitumor effect of butyrate alone, and also on expression of HSVtk gene by Western blot analysis. Then we determined the effects of butyrate on bystander-mediated cell killing in vitro. Results: There was no inhibition of growth of cells exposed to butyrate for 24 hours at a concentration of 1.5mM/L. Toxic effects were seen when the concentration of butyrate was greater than 2.0mM/L. Gene expression was more stable and bystander effect was augmented by butyrate treatment of a concentration of 1.5mM/L. Conclusion: These results provide evidence that butyrate can augment the efficiency of cell killing with HSVtk/GCV system by inducing transgene expression and may thus by a promising new approach to improve responses in gene therapy using adenoviral vectors.

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Effect of High Purity β-1.3/1.6-Glucan on Macrophages, Natural Killer Cells, and T Cell-Mediated Factors (고순도 β-1.3/1.6-Glucan이 대식세포 및 자연살해세포와 T 세포면역계에 미치는 영향)

  • Kwon, Hanol;Lee, Minhee;Park, Soo-Jeung;Lee, Dasom;Kim, Hyesook;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.11
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    • pp.1564-1570
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    • 2016
  • The present study investigated the immunomodulatory effects of high-purity ${\beta}$-1.3/1.6-glucan on macrophages, natural killer (NK) cells, and T cell-mediated factors. Effect of high-purity ${\beta}$-1.3/1.6-glucan on cytotoxicity in macrophages was investigated. Using macrophages, cytotoxicity of high-purity ${\beta}$-1.3/1.6-glucan was evaluated by MTT assay. We treated high-purity ${\beta}$-1.3/1.6-glucan at concentrations of 10, 50, 100, 150, 200, and $250{\mu}g/mL$ in macrophages. High-purity ${\beta}$-1.3/1.6-glucan did not affect macrophage viability. Phagocytic activity was assessed using zymosan. Activity of high-purity ${\beta}$-1.3/1.6-glucan on macrophages significantly increased as compared with zymosan. We treated high-purity ${\beta}$-1.3/1.6-glucan to murine NK cells co-incubated with YAC-1 cells. High-purity ${\beta}$-1.3/1.6-glucan resulted in significantly increased activity of NK cells as compared with the control. In addition, treatment of macrophages with high-purity ${\beta}$-1.3/1.6-glucan resulted in significantly increased activity of T cell-mediated cytokine (IL-2, IL-12, $IFN-{\gamma}$, and $TNF-{\alpha}$) levels and CD4+/CD8+ T cells as compared with the control. In conclusion, high-purity ${\beta}$-1.3/1.6-glucan could enhance the immune response through activation of macrophages, NK cells, and T cell-mediated factors.

Case Report of Squamous Cell Carcinoma arising in an Oral Lichen Planus and Literature Investigation (구강편평태선 환자에서 발생한 암종의 증례보고 및 문헌 고찰)

  • Lim, Hyun-Dae;Lee, You-Mee
    • Journal of Oral Medicine and Pain
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    • v.34 no.1
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    • pp.49-54
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    • 2009
  • Lichen planus is a relatively common chronic inflammatory disease involving the skin and mucous membranes showing small flat polygonal papules. The accurate etiology is unknown but it's suggested that cell-mediated immune response to an induced antigenic changes in skin or mucosa. Oral lichen planus was regarded as an benign lesion but oral lichen planus was classified as premalignant lesion by WHO criteria. It was not known that progress of malignat transmmission in the the patient with oral lichen planus, and chronic inflammatory disease including oral lichen planus showed malignacy in oral cancer unrelated common risk factors(Ex: tabacco, alcohol). Although malignant development in the patient with oral liche planus was various greatly in the literature, from 0.5% upward to 5%. It has been reported that a specific clinical type of oral lichen planus, hyperkeratotic or erosive had a higher chance of transformation into an squamous carcinoma. Clinician has to follow-up check of at least one or two visit per year to detect of malignancy of oral lichen planus and improved prognosis with squamous cell carcinoma. At this case with the middle aged women with squamous cell carcinoma developed from oral lichen planus of more than a decade of persisting, we try to discuss the malignacy of oral lichen planus and cosideration with follow-up.

The Neovascularization Effect of Bone Marrow Stromal Cells in Temporal Muscle after Encephalomyosynangiosis in Chronic Cerebral Ischemic Rats

  • Kim, Hyung-Syup;Lee, Hyung-Jin;Yeu, In-Seung;Yi, Jin-Seok;Yang, Ji-Ho;Lee, Il-Woo
    • Journal of Korean Neurosurgical Society
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    • v.44 no.4
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    • pp.249-255
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    • 2008
  • Objective : In Moyamoya disease, the primary goal of treatment is to improve collateral circulation through angiogenesis. In the present study, we obtained and sub-cultured bone marrow stromal cells (BMSCs) from rats without a cell-mediated immune response. Then, we injected the labeled BMSCs directly into adjacent temporal muscle during encephalomyosynangiosis (EMS). Three weeks after BMSC transplantation, we examined the survival of the cells and the extent of neovascularization. Methods : We divided 20 rats into a BMSC transplantation group (n=12) and a control group (n=8). Seven days after the induction of chronic cerebral ischemia, an EMS operation was performed, and labeled BMSCs ($1{\times}106^6/100\;{\mu}L$) were injected in the temporal muscle for the transplantation group, while an equivalent amount of culture solution was injected for the control group. Three weeks after the transplantation, temporal muscle and brain tissue were collected for histological examination and western blot analysis. Results : The capillary/muscle ratio in the temporal muscle was increased in the BMSC transplantation group compared to the control group, showing a greater increase of angiogenesis (p<0.05). In the brain tissue, angiogenesis was not significantly different between the two groups. The injected BMSCs in the temporal muscle were vascular endothelial growth factor (VEGF)-positive by immunofluorescence staining. In both temporal muscle and brain tissue, the expression of VEGF by western blot analysis was not much different between the two groups. Conclusion : During EMS in a chronic cerebral ischemia rat model, the injection of BMSCs resulted in accelerated angiogenesis in the temporal muscle compared to the control group.

Immunologic effects of somatic antigens of house dust mite (Dermatophagoides pteronyssinus) against canine sarcoptic mite (Sarcoptes scabiei var. canis) infestation (집먼지진드기 체항원을 이용한 개 옴 감염증에 대한 면역효과)

  • Yoon, In-Soo;Kim, Jae-Won;Jee, Cha-Ho
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.689-696
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    • 2003
  • Canine sarcoptic mite (Sarcoptes scabiei var. canis) burrow usually in the stratum corneum of the skin of dogs and rabbits. Antigens from the burrowing mites induce cutaneous inflammatory reaction and humoral and cell-mediated immune response in the host. The effect of immunization induced by somatic antigens of house dust mite (Dermatophagoides spp.) has been evaluated to control the canine sarcoptic mite in this experiment. Twelve common antigens (187, 142, 126, 120, 109, 92, 80, 68, 51, 30, 25, 17 kDa) were found using SDS-PAGE with silver staining and Western blot between canine sarcoptic mite and house dust mite. In order to evaluate the immunologic effect of these common antigens 10 New Zealand white rabbits were divided as 4 groups such as negative control (group I), positive challenged control (group II), vaccinated (group III), and vaccinated-challenged (group IV) groups. Group II was artificially infested with about 1,000 canine sarcoptic mites and group III and IV were immunized with somatic antigens of house dust mite. In addition group IV was artificially infested with about 1,000 canine sarcoptic mites and group II, IV were treated with ivermectin. At the 8 weeks of the vaccination with common antigen, the antibody titers of all groups of II, III and IV had been increased. Both infestation score and live canine sarcoptic mite counts of group IV were lower than group III. Infestation score of group II become 0 by 2 weeks and group IV by 4 weeks after infestation. These results suggest that house dust mite, which is easy to culture in vitro, can be a vaccine candidate for protection of canine sarcoptic mite infestation.

Nitric Oxide Dependency in Inflammatory Response-related Gene Transcripts Expressed in Lipopolysaccharide-treated RAW 264.7 Cells

  • Pie, Jae-Eun;Yi, Hyeon-Gyu
    • Molecular & Cellular Toxicology
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    • v.5 no.4
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    • pp.354-363
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    • 2009
  • Cytotoxic Nitric oxide (NO) overproduced by inducible NO Synthase (iNOS or NOS2), which was induced in inflammatory reactions and immune responses directly or indirectly affects the functions as host defense and can cause normal tissue damage. Microarray analysis was performed to identify gene profiles of both NO-dependent and -independent transcripts in RAW 264.7 macrophages that use selective NOS2 inhibitors aminoguanidine ($100\;{\mu}M$) and L-canavanine (1 mM). A total of 3,297 genes were identified that were up- or down-regulated significantly over 2-fold in lipopolysaccharide (LPS)-treated macrophages. NO-dependency was determined in the expressed total gene profiles and also within inflammatory conditions-related functional categories. Out of all the gene profiles, 1711 genes affected NO-dependently and -independently in 567 genes. In the categories of inflammatory conditions, transcripts of 16 genes (Pomp, C8a, Ifih1, Irak1, Txnrd1, Ptafr, Scube1, Cd8a, Gpx4, Ltb, Fasl, Igk-V21-9, Vac14, Mbl1, C1r and Tlr6) and 29 geneas (IL-1beta, Mpa2l, IFN activated genes and Chemokine ligands) affected NO-dependently and -independently, respectively. This NO dependency can be applied to inflammatory reaction-related functional classifications, such as cell migration, chemotaxis, cytokine, Jak/STAT signaling pathway, and MAPK signaling pathway. Our results suggest that LPS-induced gene transcripts in inflammation or infection can be classified into physiological and toxic effects by their dependency on the NOS2-mediated NO release.

Recent Progress in Development of Vaccines against Avian Coccidiosis (조류 콕시듐증의 백신개발에 대한 최근의 진보)

  • Lillehoj, Hyun S.
    • Korean Journal of Poultry Science
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    • v.26 no.3
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    • pp.149-170
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    • 1999
  • Protozoa of the genus Eimeria are the etiologic agents of avian coccidiosis, the most economically important Parasitic disease for the poultry industry. Coccidia multiply in intestinal epithelial cells of a wide range of hosts, including livestock in addition to poultry. Chemotherapy is extensively used to control coccidiosis. However, development of drug resistance by Eimeria parasites, the intensive cost and labor involved in the identification of new anticoccidial compounds and public awareness of drug residues in foods warrant alternative methods to prevent coccidiocic in the fast growing poultry industry. For these reasons, there is a great interest in developing vaccines against avian coccidiosis. Live Eimeria vaccines confer protective immunity, however a significant disadvantage of using these types of vaccines is their pathogenicity. Live parasites with attenuated pathogenicity also usually produce immunity but may revert back to a pathogenic form and may be contaminated with other pathogenic organisms. Killed Eimeria vaccines are safer but, unlike live attenuated vaccines, are not able to generate cytotoxic T lymphocyte responses. Recombinant vaccines are biochemically purified proteins produced by genetic engineering that consist of particular epitopes or metabolites of Eimeria. Unlike live attenuated organisms, recombinant vaccines do not possess as much risk and generally are able to induce both humoral and cell mediated immunity. DNA vaccines consist of genes encoding immunogenic proteins of pathogens that are directly administered into the host in a manner that the gene is expressed and the resulting protein generates a protective immune response. Although all of these different types of vaccines have been applied to coccidiosis, this disease continues to cause substantial morbidity and mortality in the poultry industry. Future development of an effective vaccine against coccidiosis will depend on further investigation of protective immunity to Eimeria infection and identification of important immundgenic parasite molecules.

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The Effects of New Nonspecific Immunostimulators in Pig (면역기능 증강성 신물질에 대한 돼지에서의 면역 증강성 실험)

  • Jung Ji-Youn;Ahn Nam-Shik;Park Joon-Suk;Jo Eun-Hye;Hwang Jae-Woong;Park Jung-Ran;Kim Sun-Jung;Lee Yong-Geon;Jeong Yun-Hyeok;Chung Ji-Hye;Lee Seung-Ho;Park Young-Seok;Park Byung-Kwon
    • Journal of Food Hygiene and Safety
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    • v.21 no.2
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    • pp.113-117
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    • 2006
  • New nonspecific immunostimulators (Koko enterprise Co., Ltd., Korea) were evaluated for its effectiveness as a nonspecific immunostimulator in pigs. The effects of new nonspecific immunostimulators were determined by analysis of cytokines using ELISA and blood-chemistry. IFN-r which is one of the cell mediated immune cytokines significantly increased in DIR-vitamineral 0.2% group posttreatment 4 weeks and was significantly higher IMF 0.2%, DIR-vita 0.1% and DIR-vitamineral 0.2% groups than control group in 3 months. DIR-vitamineral 0.2% had a most strong effectiveness as a nonspecific immunostimulator in our treatment materials in pigs. IMF 0.2% and DIR-vita 0.1% were seen that there had effectiveness of a nonspecific immunostimulator in posttreatment 3 months. IgG IgM and Total Ig which were humoral immune globulins, were not significantly changed in posttreatment 4 weeks and 3 months. In conclusion, this study has demonstrated that new nonspecific immunostimulators had an immunostimulatory effect on pigs through cell mediated immune response.

Dietary Brown Seaweed Modulates Nutrient Metabolism, Anti-oxidant System and Immune Response in Broiler Chicks Injected LPS i.p. (사료 중 미역은 복강내 LPS 주입 육계 병아리에서 영양소 대사, 항산화계 및 면역 반응을 조정한다)

  • Park, In-Kyung;Im, Jin-Taek;Choi, Do-Yul;Koh, Tae-Song
    • Journal of Animal Science and Technology
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    • v.50 no.2
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    • pp.185-198
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    • 2008
  • Influences of dietary brown seaweed(BSW) on the nutrient metabolism, anti-oxidant enzyme activity and cell-mediated immune response were studied in broiler chicks activated acute phase response. 72 Hatched male broiler chicks(Ross) were divided into 12 pens, 6 heads per pen, and fed the BSW 0.0% (Basal) or 2.0% diet, respectively, and injected with the Salmonella typhimurium lipopoly saccharide(LPS) for activation of the acute phase response three times at 8, 10 and 12 d of age. During 4 wks of experimental feeding, growth performance of broiler chicks was not affected by dietary BSW and the acute phase response. Compared with control birds, the acute phase response did not affect the daily weight gain in birds fed BSW 2.0% diet, decreased nitrogen balance(NB) or metabolizable energy(ME) utilization per metabolic body size(kg0.75), and enhanced activities of peroxidase or extracellular SOD(EcSOD), tumor necrosis factor-alpha and ovotransferrin in plasma and MnSOD and CuZnSOD in erythrocyte cytosol. Compared to BSW 0.0% diet, 2.0% diet enhanced protein retention(NB) per kg0.75 regardless the acute phase response, did not affect uric acid nitrogen excretion(UAN) per kg0.75 in birds during the acute phase response, decreased(p<0.05) the UAN excretion per kg0.75 in control birds. And BSW 2.0% diet also decreased(p<0.05) plasma peroxide level and erythrocyte peroxidase or MnSOD activity but increased plasma peroxidase and EcSOD activity and interleukin-1 activity secreted from LPS-stimulated PBMC in 4 week broiler chicks.