• IMMUNE NETWORK
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• v.1 no.3
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• pp.230-235
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• 2001

Background: Finding of the regulation of various gene expression by cytokine including $IFN-{\gamma}$ in hematopoietic stem cell will light up the understanding of pathogenesis of aplastic anemia in various aspects. To study on aplastic anemia, however, we have to circumvent the difficulty of directly obtaining bone marrow stem cells from the patient. Therefore, we tried to find out a cell can replace the bone marrow stem cells for study on cell signaling pathway and regulation of gene expression by $IFN-{\gamma}$. Materials and Methods: HL-60 cells, of 20 ng/mL of $IFN-{\gamma}$. Total RNA was isolated from the cells and RT-PCR of the indoleamine 2,3-dioxygenase (IDO), $IFN-{\gamma}$, TNF-${\alpha}$, $MIP-1{\alpha}$, and $TGF-{\beta}2$ was carried out for the estimation of the gene expression. Results: $IFN-{\gamma}$ induced IDO gene expression of mononuclear cells from umbilical cord blood showed similar pattern as compared to that of bone marrow. Whether $INF-{\gamma}$ was treated or not, $TNF-{\alpha}$ was expressed in both mononuclear cells from umbilical cord blood and bone marrow. However, HL-60 cells showed different expression patterns. HL-60 cells would express neither IDO nor $TNF-{\alpha}$ even under the culture with 20ng/mL of $IFN-{\gamma}$. Conclusion: Our results showed bone marrow can be replaced with mononuclear cells from umbilical cord blood in the study on the relation between aplastic anemia and $IFN-{\gamma}$ including $IFN-{\gamma}$ cell signaling pathway.

• Biomedical Science Letters
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• v.5 no.1
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• pp.85-93
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• 1999

Nitric oxide (NO) plays an important role in immunologic defense, and influences upon the functioning of secretory tissues and cells. It also exhibits cytotoxic/cytostatic activity as one of major operating effectors of the cellular immunity system. We investigated the effects of serum on the cell damages and NO production in the mouse liver cell line BNL CL.2 to establish the role of NO. We observed that, when BNL CL.2 cells were cultured in serum-free medium, they were induced to cell damage by the stimulation of IFN-$\gamma$ alone or IFN-$\gamma$ plus LPS. Serum-starved cells showed large amount of nitrite accumulation and NO synthase (NOS) expression in response to IFN-$\gamma$ alone in dose- and time- dependent manners, but serum-supplied cells did not The production of NO was blocked by protein tyrosine kinase (PTK) inhibitors, genistein and herbimycin. These results suggest that the deprivation of serum in the BNL CL.2 cell culture medium might primed with the cells to produce NO when the cells are triggered by IFN-$\gamma$ and the involvement of PTK signal transduction pathway in the expression of NOS gene in murine hepatocytes.

• BMB Reports
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• v.45 no.5
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• pp.281-286
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• 2012

Osteoclasts are multinucleated cells that are formed by the fusion of pre-fusion osteoclasts (pOCs). The fusion of pOCs is known to be important for osteoclastic bone resorption. Here, we examined the effect of IFN-${\gamma}$ on the fusion of pOCs. IFN-${\gamma}$ greatly increased the fusion of pOCs in a dose-dependent manner. Furthermore, IFN-${\gamma}$ induced pOC fusion even in hydroxyapatite-coated plates used as a substitute for bone. The resorption area of pOCs stimulated with IFN-${\gamma}$ was significantly higher than that of the control cells. IFN-${\gamma}$ induced the expression of dendritic cell-specific transmembrane protein (DC-STAMP), which is responsible for the fusion of pOCs. IFN-${\gamma}$ enhanced DC-STAMP expression in a dose-dependent manner. The mRNA expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 was enhanced in the pOCs treated with IFN-${\gamma}$. Taken together, these results provide a new insight into the novel role of IFN-${\gamma}$ on the fusion of pOCs.

• Proceedings of the Korea Society of Poultry Science Conference
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• 1999.11a
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• pp.34-50
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• 1999

A cDNA encoding chicken interferon-gamma (chIFN-${\gamma}$) was amplified from P34, a CD4$^{+}$ T-cell hybridoma by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into pUC18. THe sequences of cloned PCR products were determined to confirm the correct cloning. Using this cDNA as probe, chicken genomic library from White Leghorn spleen was screened. Phage clones harboring chicken interferon-gamma (chIFN-${\gamma}$) were isolated and their genomic structure elucidated. The chIFN-${\gamma}$ contains 4 exons and 3 introns spanning over 14 kb, and follows the GT/AG rule for correct splicing at the exon/intron boundaries. The four exons encode 41, 26, 57 and 40 amino acids, respectively, suggesting that the overall structure of IFN-${\gamma}$ is evolutionairly conserved in mammalian and avian species. The 5’-untranslated region and signal sequences are located in exon 1. Several AT-rich sequences located in the fourth exon may indicate a role in mRNA turnover. The 5’-flanking region contains sequences homologous to the potential binding sites for the mammalian transcription factors, activator protein-1(AP-1) activator protein-2(AP-2) cAMP-response element binding protein(CREB), activating transcription factor(ATF), GATA-binding fator(GATA), upstream stimulating factor(USF), This suggests that the mechanisms underlying transcriptional regulation of chicken and mammalian IFN-${\gamma}$ genes may be similar.r.

• Journal of Life Science
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• v.23 no.9
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• pp.1140-1146
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• 2013

The effect of dried mackerel extract on the production of nitric oxide (NO) and cytokines, including interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was investigated. All extracts and fractions from dried mackerel significantly reduced NO production induced by lipopolysaccharide (LPS). Among the extracts, acetone+methylene chloride (A+M), n-hexane, and 85% aqueous methanol (MeOH) showed the strongest inhibitory effects. The 85% aqueous MeOH fraction at a concentration of $10{\mu}g$ significantly decreased LPS-induced IL-6 and TNF-${\alpha}$ production after 6 hr of incubation. In the case of LPS-induced IFN-${\gamma}$ production, the 85% aqueous MeOH fraction decreased the production of IFN-${\gamma}$ afer 6, 24, and 72 hr of incubation in a dose-dependent manner. The results show that an 85% aqueous MeOH fraction inhibits the production of NO and proinflammatory cytokines (IL-6, TNF-${\alpha}$, IFN-${\gamma}$), suggesting that this fraction acts as a potent immunomodulator.

• Archives of Pharmacal Research
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• v.22 no.3
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• pp.267-273
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• 1999

In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with $IFN-\gamma$. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-, had a very low activating effect. Following preincubation with both protein A and $IFN-\gamma$, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-$\alpha$ or the inhibition of NO Production, TNF-$\alpha$ and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with $IFN-\gamma$. We also demonstrated that supernatants from macrophages treated with protein A plus $IFN-\gamma$ contained both TNF-$\alpha$ and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-$\alpha$ or NO. These results demonstrate the synergistic effects on mouse pertioneal macrophage function of protein A in combination with $IFN-\gamma$ and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.

• Proceedings of the Ginseng society Conference
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• 2006.05a
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• pp.83-88
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• 2006

In this study we examined the potential for the synergistic augmentation of the activity of inflammatory mouse peritoneal macrophages by stimulation with RGAP combined with IFN-$\gamma$. The moderate augmentative effect induced by preincubation with RGAP was observed in the production of IL-1, IL-6 and NO but not TNF-$\alpha$. In addition, IFN-$\gamma$ had a low activating effect. Following preincubation with both RGAP A and IFN-$\gamma$, a marked enhancement of secretory activity and tumoricidal activity was noted in mouse peritoneal macrophages. Treatment of peritoneal macrophage with combination increased the generation of IL-1, IL-6, TNF-$\alpha$ and NO, whereas the production of reactive oxygen species were not altered. These results demonstrate the synergistic effects on macrophage function of RGAP in combination with IFN-$\gamma$ and suggest that the ability of IFN-$\gamma$ to prime macrophages to produce secretory molecules in response to RGAP may have implications for immunotherapy with this combination.

• Parasites, Hosts and Diseases
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• v.38 no.2
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• pp.85-90
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• 2000

To assess the relationship between the changes of cellular components and the production of Th 1 cytokine in the immune tissue, inbred C57BL/6 mice were orally infected with 40 cysts of 76K strain of Toxoplosma gondii. The sequential change of cell differentials and $IFN-{\gamma}$ production of splenocytes were analyzed by Diff-Quik stain and RT-PCR. There were no significant proportional changes of cellular components of splenocytes until day 4 postinfection (Pl) as compared to those of day 0, and the relative percentage of macrophages and neutrophils/eosinophils increased significantly (p<0.01) thereafter. The expression of $IFN-{\gamma}$ mRNA of $CD3^{-}$ cells was observed from day 1 Pl at a low level. However, $IFN-{\gamma}$ production of $CD3^{+}$ cells increased significantly from day 4 Pl (p<0.01) which progressively increased thereafter. These findings provide the relative percentages of granulocytes and macrophages were increased in conjunction with increase of total number of splenocytes after oral infection with T. gondii in the susceptible murine hosts, and lymphocytes were the major cellular components and the important source of $IFN-{\gamma}$.

• Animal cells and systems
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• v.8 no.2
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• pp.117-123
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• 2004

The purpose of this study was to analyze inhibitory effects of anti-4-1BB monoclonal antibody on melanoma metastasis The 4-1BB (CD137) T cell molecule is a member of the TNF receptor family and its activation by either 4-1BB ligand or antibody induces T cell activation and growth. In the present study, administration of anti-4-1BB mAb induced inhibition of melanoma metastasis. Agonistic anti-4-1BB mAb induced not only CD$8^+$4-1BBT cells but also CD$8^+$IFN-${\gamma}$$^{+}$ T cell population. In the presence of anti-CD3 antibody, lymphocytes produced high levels of IFN-${\gamma}$ and low levels of IL-4 in anti-4-1BB mAb treated group. Exposure of melanoma cells to IFN-${\gamma}$ induced expression of MHC-I molecules. Thus, the increase in number of CD$8^+$T cells and enhanced MHC-I expression on B16F10 cells by augmented IFN-${\gamma}$ production in response to anti-4-1BB mAb may result in suppression of tumor growth and metastasis.s.

• The Korean Journal of Food And Nutrition
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• v.20 no.3
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• pp.259-264
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• 2007

Ginger(Zingiber officinale Roscoe) has been used as a raw material in many various traditional preparations since the ancient times. As a component of traditional health products, ginger is known to be effective as an appetite enhancer, and has anti-cold and anti-inflammatory activities. This study was performed to investigate the immunomodulative effects of Zingiber officinale Roscoe in mice, using ex vivo experiments. In order to elucidate ginger's immunomodulative effects of Ginger, water extracts were orally administered to mice, and isolated macrophages were used as the experimental model. To identify the ex vivo effects, six to seven week old Balb/c mice were fed a chow diet ad libitum and the ginger water extracts were administered orally every other day for two or four weeks at two different concentrations(50 and 500 mg/kg b.w.). The results show that IL-IO and $IFN-{\gamma}$ were detected in the 500 mg/kg b.w. supplemented group with LPS stimulation in all cases. Also, the $IFN-{\gamma}$ /IL-10 ratio ranged from 3~5 with mitogen stimulation such as Con A and LPS. In conclusion, this study suggests that ginger extracts may enhance the immune function by regulating the cytokine(IL-10 and $IFN-{\gamma}$) production capacity of activated macrophages in mice.