• 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.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5513-5518
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• 2013

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

• Journal of Oriental Neuropsychiatry
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• v.15 no.2
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• pp.89-101
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• 2004

Objective : The present experiments were designed to study on the immune-enhancing effect of Mountain grown ginseng, Mountain cultivated ginseng, and Panax ginseng Method : In order to compare the immune-enhancing effect of moutain grown ginseng, moutain cultivated ginseng and Panax ginseng, the study was done through the forced swimming test (FST), measurement of T helper Th1, Th2 cytokines and fatigue related factors. Result : Moutain grown ginseng and panax ginseng decreased the immobility time in the FST compared to the control. Glucose, blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH) and Total-protein (T-protein) in serum were investigated. The serum achieved from ginseng administered mouse showed higher BUN, T-protein than the control. moutain grown ginseng administered group showed lower LDH than the control group. moutain grown ginseng administered mouse showed higher glucose than the control. Creatinine was same in either experimental or control group. Ginseng-induced cytokine production in human T-cell line, MOLT-4 cells and mouse peritoneal macrophages were compared. Moutain cultivated ginseng (10-4 dilution) and panax ginseng (10-3 dilution) were increased the interferon $IFN-{\gamma}$ production compared with media control (about 1.6-fold P<0.05) at 48 h. Moutain grown ginseng (10-4 dilution) was increased the $IFN-{\gamma}$ and interleukin IL-4 production compared with media control (about l.4-fold for $IFN-{\gamma}$ and 1.6-fold for IL-4 P<0.05) at 48 h. Moutain grown ginseng (10-3 dilution) and moutain cultivated ginseng (10-4 dilution) were increased the turmor necrosis factor $TNF-{\alpha}$ production compared with $rIFN-{\gamma}$ treated cells (about 1.9-fold for $TNF-{\alpha}$ P<0.05), respectively. Moutain cultivated ginseng (10-3 dilution) was increased the IL-12 production compared with $rIFN-{\gamma}$ treated cell (about 1.7-fold for IL-12 P<0.05). Conclusion : These data suggest that three different three kinds of ginseng act on immune responses in different aspects.

• IMMUNE NETWORK
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• v.16 no.2
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• pp.109-115
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• 2016

To find the relation between exercise and cytokines, we examined the effect of the training intensity on the levels of cytokines, including interferon-gamma (IFN-γ), interlukine-4 (IL-4) and interlukine-4/interferon-gamma ratio (IL-4/IFN-γ ratio) in female Futsal players. Twelve well-trained female college Futsal players aged 19~22 participated in this study. The athletes completed 30-min of running at 60~65% maximal heart rate [moderate-intensity exercise], and 30-min of running at 75~80% maximal heart rate [high-intensity exercise]. peripheral blood samples were collected 24 h before and 24 h and 48 h after each of the exercise bouts. finding showed that The 30-min bout of moderate-intensity exercise induced a significant increase in IFN-γ (p=0.01) and significant decreases in IL-4 (p=0.001) and IL-4/IFN-γ ratio (p=0.003). And also, 30-min of running at 75~80% maximal heart rate induced increase in IFN-γ (p=0.07) and decreased in IL-4 (p=0.01) and IL-4/IFN-γ ratio (p=0.06) that these changes not significantly. In summary, exercise intensity can effect on the magnitude of changes in cytokines. It seems that moderate intensity exercise enhances cytokine pattern in female college Futsal players.

• Parasites, Hosts and Diseases
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• v.40 no.3
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• pp.119-129
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• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.406-412
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• 2005

Background : Recently, two commercialized whole-blood assays, $QuantiFERON^{(R)}-TB$ Gold (QFT) and T $SPOT-TB^{(R)}$ (SPOT), which measure the $IFN-{\gamma}$ released in the whole blood after being incubation with mycobacterial antigens, were approved for the diagnosis of a latent tuberculosis infection (LTBI). However, there is data on whether or not the previously used PPD skin tests (TST) have any influence on the diagnostic ability of these ex-vivo $IFN-{\gamma}$ assays. Methods : Forty-six 15 year-old students who did not appear to be infected with Mycobacterium tuberculosis were enrolled in this study. The peripheral blood was collected and used for two $IFN-{\gamma}$ assays. The $IFN-{\gamma}$ assays and TST were performed at the baseline ($1^{st}$). The TST was repeated two months later ($2^{nd}$), and the $IFN-{\gamma}$ assays were repeated two ($2^{nd}$) and four months ($3^{rd}$) later only in those subjects who had negative results at the baseline in both the $IFN-{\gamma}$ assays and TST. An induration size > 10 mm was considered to be positive in the TST. Results : The mean TST value was $3.1{\pm}5.4mm$ (range: 0-20). Of the 46 subjects examined, 13 subjects (28.3%) showed positive results in the two-step TST. Nine (19.6%) were SPOT-positive and only one (2.2%) was QFT-positive. The $2^{nd}$ and $3^{rd}$ QFT were carried out in 23 and 25 all-negative subjects, respectively, and all showed negative results. The $2^{nd}$ SPOT was performed in 23 subjects and only one (4.3%) showed a weak-positive result. Conclusion : Even though there were some discrepancies in the results of the two ex-vivo $IFN-{\gamma}$ assays, it appears that their results were not influenced by a previous TST carried out in two or four months earlier.

• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.611-618
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• 2004

Background : Idiopathic pulmonary fibrosis(IPF), a subtype of IIP(idiopathic interstitial pneumonia), is a fatal disease with a 3-5 year median survival. Many attempts at treating this condition have failed to demonstrate a survival benefit in IPF. Recently Ziesche et $al^{12}$ reported the efficacy of IFN-${\gamma}$ for treating IPF but there is still some controversy. The aim of this study was to determine the efficacy of IFN-${\gamma}$ in patients with advanced IPF who had not been responsive to steroid and cytotoxic agents. Method : Nine patients with advanced IPF(age: $55.4{\pm}15.3$ years, Male: Female=8:1) were enrolled. One year treatment regime with 2 million IU of IFN-${\gamma}$ administered subcutaneously three times a week, and low dose prednisolone(10-30 mg/d) was also used. In the case of a definite aggravation and serious side effects, the IFN-${\gamma}$ was discontinued. During the IFN-${\gamma}$ trial, a pulmonary function test and chest radiography were checked every three month throughout the study. Result : 1) Among 9 patients, only 4 patients were able to complete the 12 month treatment with IFN-${\gamma}$, and 5 patients died during the treatment period. 2) No improvement either in the respiratory symptoms or pulmonary functions were observed any of the patients, even in those who completed the 12 months trial of IFN-${\gamma}$, 3) At the time of IFN-${\gamma}$ trial, the survivors who finished the IFN-${\gamma}$ treatment for 12 months had a higher oxygen level($81.3{\pm}2.8$ vs. $67.4{\pm}8.4$, P=0.024) and a better pulmonary function(FVC: $61.3{\pm}5.1$ % predicted vs. $45.7{\pm}12.3%$, P=0.048, and $D_Lco$: $45.0{\pm}5.0%$ predicted vs. $30.8{\pm}11.2%$, P=0.048) than the non-survivors. Conclusion : Our data suggested that IFN-${\gamma}$ therapy was not effective in the patients with advanced IPF refractory compared with other therapeutic agents. Furthermore, these results suggest that severe impairment of the pulmonary function and hypoxemia during the IFN-${\gamma}$ therapy requires special attention.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.130-136
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• 1999

Mouse guanylate-binding protein 3 (mGBP3) is a 71-kDa GTPase which belongs to GTP-binding protein family. The present study showed that the expression of mGBP3 transcript was readily induced in a dose dependent fashion in the macrophage cell line RAW264.7 treated with either $interferon-{\gamma} (IFN-\gamma)$ or lipopolysaccaride (LPS). The expression of mGBP3 protein was also apparent by 4 and 6 h after the treatment of cells with IFN-\gamma (100 U/ml) or LPS ($1{\mu}g/ml$) , and remained at palteau for at least 24 h. Cycloheximide ($10{\mu}g/ml$) had no effect on the $IFN-\gamma-$ or LPS-induced mGBP3 expression, suggesting that the mGBP3 induction did not require further protein synthesis. Interestingly, a protein kinase C (PKC) inhibitor staurosporine (50 nM) abolished the induction of mGBP3 expression by LPS, but not by $IFN-{\gamma}$. These findings suggest that mGBP3 may be involved in the macrophage activation process and both IFN-\gamma and LS induce the mGBP3 expression through distinct signal transduction pathways.

• Tuberculosis and Respiratory Diseases
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• v.73 no.3
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• pp.143-150
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• 2012

Background: The release of interferon-gamma (IFN-${\gamma}$) by T lymphocytes increases after rechallenge with Mycobacterium tuberculosis antigen, especially, at a localized site of tuberculosis (TB) infection. We aimed to compare the clincial efficacy of two commercial IFN-${\gamma}$ release assays from pleural fluid for the diagnosis in tuberculous pleurisy. Methods: We performed T-SPOT.TB and QuantiFERON-TB Gold tests simultaneously on pleural fluid and peripheral blood samples from patients with pleural effusion, in South Korea, an area with intermediate TB burden. Results: Thirty-six patients were enrolled prospectively, and tuberculous pleurisy was found in 21 patients. Both the numbers of IFN-${\gamma}$ secreting T cells and the concentration of IFN-${\gamma}$ were greater in the pleural tuberculous group, comparing with the non-tuberculous group. Moreover, in the tuberculous group, there was a significant difference in IFN-${\gamma}$ producing spot-forming cells using the T-SPOT.TB method between pleural fluid and peripheral blood. The receiver operating characteristic (ROC) curve, was the greatest for pleural fluid T-SPOT.TB test, followed by peripheral blood T-SPOT.TB test, peripheral blood QuantiFERON-TB Gold test, and pleural fluid QuantiFERON-TB Gold test (area under the ROC curve of 0.956, 0.890, 0.743, and 0.721, respectively). The T-SPOT.TB assay produced less indeterminate results than did QuantiFERON-TB Gold assay in both pleural fluid and peripheral blood. Conclusion: These findings suggest that the pleural fluid T-SPOT.TB test could be the most useful test among the IFN-${\gamma}$ release assays for diagnosing tuberculous pleurisy in an area with an intermediate prevalence of TB infection.