• 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.

• 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.

• Parasites, Hosts and Diseases
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• v.34 no.3
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• pp.185-190
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• 1996

The TH cytokine responses of spleen cells stimulated with Con A from mice infected with Polasonimw westemcni were examined. The spleen cell culture supema- tants were assayed for TH1-specific $IFN-{\gamma}$ and TH2-specific IL-4. Cytokine responses for IL-4 peaked at three days ($410{\;}{\pm}{\;}60.9{\;}pg/ml$), persisted at a high level until the second week ($343{\;}{\pm}{\;}59.0{\;}pg/ml$), and then decreased slowly four and six weeks after infection. $IFN-{\gamma}$ production by splenocytes only increased during the first week ($151{\;}{\pm}{\;}32.3{\;}pg/ml$) and declined abruptly after the second week of infection. IFN- y production by splenocytes of infected mice was not observed during the sixth week of infection. In addition, serum IL-4 and $IFN-{\gamma}$ were measured. Serum IL-4 was not detected in substantial quantity until four to six weeks after infection. The time course of serum IL-4 was not correlated with that of IL-4 production by splenocytes. Serum $IFN-{\gamma}$ was undetectable during the entire course of infection. These results suggest that TH2 cytokine responses, rather than TH1, predominate in mice infected with P. westemcni.

• Environmental Analysis Health and Toxicology
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• v.20 no.3 s.50
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• pp.243-248
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• 2005

Mancozeb (MCZ), a polymeric complex of zinr and manganese salts of ethylene bisthiocarbamate, is widely used in agriculture as fungicidel, insecticides, and herbicides. MCZ can be occupationally and environmentally exposed to human and has been reported to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine splenocytes through evaluation of splenocytes cellularity and INF-$\gamma$ synthesis. Splenocytes were examned ex vivo from mice orally treated with various doEes of MCZ for 1 day (acute exposure, 2,100, 5,000, 10,000 mg/kg) or ior 5 consecutive days per week for 4 weeks (subacute exposure,250, 1,000, 1,500 mg/kg/day) fellowed by culture for 2 days in the presence of Con A or PHA plus IL-2. Splenocytes Iron naive mice were cultured with various concentration of MCZ (50, 500, 1,000 ng/ml) in the presence of Con A or PHA plus IL-2 for 2 days in vitro. IFN-$\gamma$ production was decreased with the in vitro exposure to all concentration of MCZ. The spleen cellularity and IFN -$\gamma$ production by splenocytes from MCZ -acutely and - subacutely exposured mice were decreased in comparision with that oi control group.

• 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.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.10
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• pp.1399-1405
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• 2013

The present study focused on establishing the effects of interferon-gamma (IFN-${\gamma}$) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in pregnant rats. Pregnant rats at the post-implantation stage were randomized into control, low IFN-${\gamma}$ (L-IFN-${\gamma}$) and high IFN-${\gamma}$ groups (H-IFN-${\gamma}$) that received normal saline, 100 IU/g of IFN-${\gamma}$ and 500 IU/g of IFN-${\gamma}$ vaginal muscular injection, respectively. The effects of IFN-${\gamma}$ on IL-18 expression and pregnancy outcomes were assessed systematically using several methods, including immunohistochemistry streptavidin-perosidase (SP), image pattern analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC) count, microscopy and visual observation. IL-18 was detected in the uteri of all pregnant rats, and mainly distributed in the endometrium, decidual cells, vascular endothelium and myometrium. Immunohistochemistry and image pattern analyses revealed significantly lower IL-18 expression in the H-IFN-${\gamma}$ group compared to the L-IFN-${\gamma}$ and control groups (p<0.01), indicating that high doses of IFN-${\gamma}$ induce downregulation of IL-18 in the uterus of pregnant rats. ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN-${\gamma}$ group was lower than that of the L-IFN-${\gamma}$ group (p<0.05), and significantly reduced compared to the control group (p<0.01). Moreover, the number of peripheral leukocytes in the H-IFN-${\gamma}$ group was significantly higher than those in the control and L-IFN-${\gamma}$ groups (p<0.01). Morphology analysis showed no evident differences between the L-IFN-${\gamma}$ and control groups. However, for the H-IFN-${\gamma}$ group, uterine mucosa bleeding, necrosis and excoriation were observed using microscopy. Visual observation revealed marroon, swelling, crassitude and no embryo in the uterus, which are obvious indicators of abortion. These results indicate that IFN-${\gamma}$ plays a regulatory role in IL-18 expression in the uterus and peripheral blood of pregnant rats at the post-implantation stage. Moreover, high levels (500 IU/g) of IFN-${\gamma}$ influence normal pregnancy at the early stages in rats by downregulating IL-18 expression in the uterus and peripheral blood and increasing the number of peripheral leukocytes, consequently triggering termination of pregnancy.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.310.3-311
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• 2002

Macrophages have been known to play an essential role in tumor angiogenesis and produce a number of growth stimulators and inhibitors. Thus macrophages appear to influence every stage of angiogenesis. In this report, TNF-$\alpha$ was able to induce the production of IFN-${\gamma}$ in cancer cell-contanted macrophage. TNF-${\gamma}$ alone released relatively little IFN-${\gamma}$ whereas live tumor cells (3LL) alone releasd IFN-${\gamma}$ markedly from macrophage. (omitted)

• Journal of Life Science
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• v.19 no.3
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• pp.411-416
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• 2009

Chitosan is derived from chitin by a process of controlled deacetylation. In the present study, we investigated the effects of chitosan on the production of cytokines such as interleukin-2 (IL-2), interferon-$\gamma$ (IFN-$\gamma$), interleukin-4 (IL-4), and interleukin-10 (IL-10) in mice. The culture supernatants of splenocytes exposed with chitosan alone or chitosan plus cell stimulants, lipopolysaccharide (LPS), concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) were harvested to assay IL-2, IFN-$\gamma$, IL-4, and IL-10 production. IL-2, IFN-$\gamma$, and IL-4 from splenocytes exposed to chitosan showed a greater increase compared to the PBS control group. IL-2 and IFN-$\gamma$ levels in the culture supernatants from splenocytes exposed to LPS+chitosan were higher than those of the groups exposed to LPS alone. IL-4 and IL-10 levels in the culture supernatants from splenocytes exposed to LPS+chitosan were lower than those of the groups exposed to LPS only. These findings demonstrate that chitosan upregulates the immune responses by Th1 cytokines (IL-2 and IFN-$\gamma$) and downregulates those by Th2 cytokines (IL-4 and IL-10) in LPS-associated immunity. These results show the potential of its usefulness for balancing the Th1/Th2 immune response, if more research results were accumulated.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.78-78
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• 1995

Increasing evidence indicates that the production of nitric oxide (NO) by inducible NO synthase (NOS) is tightely regulated. Transforming growth factor-${\beta}$ (TGF-${\beta}$) is a homodimeric protein secreted during macrophage activation, but several lines of evidence suggest that TGF-${\beta}$ is selectively suppressive for macrophage NO production. We therefore reasoned that a strategy employing oligodeoxynucleotides(ODNs) complemently to TGF-${\beta}$ mRNA (antisense ODNs) might increase NO production in IFN-${\gamma}$-treated murine peritoneal macrophages. To evaluate this concept, we tested the effects of antisense ODNs targeted to TGF-${\beta}$ mRNA (25-mer ODNs complemently to TGF-${\beta}$mRNA sequences) by introducing it into the medium of cultured macrophages. Phosphorothiolation of ODNs were employed to retard their degradation. Antisense ODNs had no effect on NO production by itself, whereas IFN-${\gamma}$ alone had modest effect. When antisense ODNs were used in combination with IFN-${\gamma}$, there was a marked cooperative induction of NO production, These effects of antisense ODNs were associated with decreased TGF-${\beta}$ expression in activated macrophages. ODNs with the same nucleotides but a scrambled sequence had no effect. Adding anti-TGF-${\beta}$ antibodies to the IFN-${\gamma}$-treated macrophages mimicked the positive effect of antisense ODNs on NO production. In addition, the effects of either antisense ODNs or anti-TGF-${\beta}$ antibodies were blocked by adding TGF-${\beta}$ in cultured macrophages. These results indicate that the generation of TGF-${\beta}$ by activated macrophages provides a self-regulating mechanism by which the temporal and perhaps spatial production of NO, a reactive and potentially toxic mediator, can be finely regulated.