• Journal of Mushroom
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• v.11 no.2
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• pp.92-98
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• 2013

This study was carried out to evaluate the immunomodulatory capacity of edible mushrooms, including Sarcodon aspratus, Letinus edodes and Grifola frondosa in mice. BALB/c mice were administered 50, 500, and 1000 mg/kg body weight of various mushrooms five times a week over 4 weeks through oral administration. The control mice were administered distilled water. No significant changes in body weight were observed. IL-4 and $IFN{\gamma}$ production was evaluated with splenic T lymphocytes stimulated in vitro with phytohemagglutinins for 48 hr. The mice group administered Sarcodon aspratus, Grifola frondosa tend to higher ratio of $IFN{\gamma}$ versus IL-4 than the other groups. In addition, the ratio of plasma IgG2a versus IgG1 was also elevated in mice treated with Sarcodon aspratus. These results indicated that Sarcodon aspratus can enhance type-1 helper T cell-mediated cellular immunity. And also, S. aspratus seems to be one of the most useful mushrooms for immunomedicine.

• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.199-210
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• 2003

Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.

• Journal of Microbiology and Biotechnology
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• v.16 no.10
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• pp.1605-1612
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• 2006

Interleukin (IL)-18, a member of the family of IL-l cytokine, is one of the principal inducers of $interferon-{\gamma}(IFN-{\gamma})$ in T lymphocytes and natural killer cells. The objective of the present study was to evaluate the effect of IL-18 on the expression of chemokine IP-10 (CXCL-10) mRNA in mouse peritoneal macrophages. IL-18 had very weak direct effect or synergistic effect with IL-12 on the expression of IP-10 mRNA in C57BL/6 mouse peritoneal macrophages. However, IL-18 pretreatment was found to playa cooperative role in the expression of lipopolysaccharide (LPS)-induced IP-10 mRNA. For the expression of LPS-induced IP-10 mRNA, the synergistic effect was detected after 16 h of IL-18 pretreatment prior to LPS stimulation. The expression level of CD14 in cells stimulated with LPS was not changed by IL-18 pretreatment, and the level of $IFN-{\gamma}$ production during IL-18 pretreatment plus LPS stimulation was barely discernible ($0.36{\pm}0.31pg/ml$). Namely, the synergistic effect of IL-18 pretreatment was not related to a change of LPS receptor, CD14 expression, and the production of $IFN-{\gamma}$ by the interaction between IL-18 and LPS. The synergistic effect of IL-18 pretreatment on the expression of LPS-induced IP-10 was related to not NF-kB but AP-1 activation, and associated with the extracellular signal-regulated kinase (ERK) pathway, one of the mitogen-activated protein kinase signaling pathways. These results provide useful information that may elucidate the mechanisms underlying the effect of IL-18 on the expression of IP-10 mRNA.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5767-5772
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• 2014

Background and Aim: B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms. Methods: PMA induced THP-1-derived macrophages or human monocyte-derived macrophages were treated with recombinant IL-12 (rIL-12) or infected with adenovirus carrying human IL-12 gene (Ad-IL-12-GFP) for 24 h, then cocultured with the SKOV3 ovarian cancer cell line for another 24 h. Macrophages were collected for real-time PCR and Western blot to detect the expression of B7-H1, and activation of the NF-${\kappa}B$ signaling pathway. Moreover, supernatants were collected to assay for IL-12, IFN-${\gamma}$ and IL-10 by ELISA. In addition, monocyte-derived macrophages treated with IFN-${\gamma}$ were cocultured with SKOV3 and determined for the expression of B7-H1. Furthermore, the expression of B7-H1 in monocyte-derived macrophages was also evaluated after blocking NF-${\kappa}B$ signaling. Results: The expression of B7-H1 was significantly upregulated in monocyte-derived macrophages treated with rIL-12 or Ad-IL-12-GFP compared with the control groups (p<0.05), accompanied by a remarkable upregulation of IFN-${\gamma}$ (p<0.05), a marked downregulation of IL-10 (p<0.05) and activation of NF-${\kappa}B$ signaling. However, the upregulation of B7-H1 was inhibited by blocking the NF-${\kappa}B$ signaling pathway (p<0.05). Expression of B7-H1 was also increased (p<0.05) in monocyte-derived macrophages treated with IFN-${\gamma}$ and cocultured with SKOV3. By contrast, the expression of B7-H1 in THP-1-derived macrophages was significantly decreased when treated in the same way as monocyte-derived macrophages (p<0.05), and IL-10 was also significantly decreased but IFN-${\gamma}$ was almost absent. Conclusions: IL-12 upregulates the expression of B7-H1 in monocyte-derived macrophages, which is possible though inducing the secretion of IFN-${\gamma}$ and further activating the NF-${\kappa}B$ signal pathway. However, IL-12 downregulates the expression of B7-H1 in THP-1-derived macrophages, associated with a lack of IFN-${\gamma}$ and inhibition of expression of IL-10.

• Parasites, Hosts and Diseases
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• v.54 no.6
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• pp.719-724
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• 2016

The present study was designed to assess the dynamic patterns of pro-inflammatory cytokines, including $IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6, acute phase protein (${\alpha}1$-acid-glycoprotein, AGP), and an inflammation associated factor (adenosine deaminase; ADA) following experimental caprine coccidiosis. Ten kids aging from 2 to 4 months were infected orally with $5{\times}10^4$ sporulated oocysts and 10 animals served as controls. Blood samples were collected in both groups before infection and at days 3, 7, 14, 21, 28, and 35 post-infection (PI), and the levels of above-mentioned factors were measured. $IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6, AGP, and ADA activities were significantly higher in infected animals from day 7 PI (P<0.05). In conclusion, the circulatory levels of most systemic inflammatory markers, including pro-inflammatory cytokines ($IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6), AGP, and ADA increased significantly starting from day 3 to day 7 PI in caprine coccidiosis.

• 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.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.211-218
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• 2010

Acanthopanax koreanum Nakai (Araliaceae) is a medicinal plant indigenous to Korea. The root and stem barks of Acanthopanax species have been used as a tonic and sedative as well as in the treatment of rheumatism and diabetes. In our study, three lignans, eleutheroside E (EE), tortoside A (TA), and syringaresinol (SY), were isolated from the stem and root of A. koreanum in an effort to study the immunomodulating effect. We treated natural killer cells and dendritic cells with lignans (EE, TA, or SY), and analyzed their cytokine (IL-12 and IFN-${\gamma}$) secretion. EE, TA, or SY markedly enhanced IL-12 secretion in mouse lymphoid (DC1) and myeloid type (DC2.4) dendritic cells after 48 hr of treatment. There were no significant differences in the cytokine stimulatory effects between EE, TA, or SY. Moreover, treatment of EE, TA, or SY significantly induced IFN-${\gamma}$ secretion by human NK cells (NK92MI) confirmed by ELISA assay. This study suggests that lignans from A. koreanum modulate cytokines, and that such modulation may provide the mechanism of action for many of their therapeutic effects.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.258-264
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• 2002

Zinc plays an important role in immunobiological responses, while excessive zinc attenuates immune functions in a dose-dependent manner. Zinc excess has been reported to increase levels of plasma prostaglandin E$_2$ (PGE$_2$), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inflammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE$_2$ synthesis, on the proinflammatory cytokine and lymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered i.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$ levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1$\beta$. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-${\gamma}$ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-${\gamma}$ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-1$\beta$ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN-${\gamma}$ but not IL-2.

• The Korean Journal of Food And Nutrition
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• v.24 no.1
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• pp.65-70
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• 2011

This study was performed to investigate the in vitro effect of a corn water extract on immune function. Splenocyte proliferation was determined by the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl terazolium bromide) assay after preparing asingle cell suspension. Production of macrophage-secreted interleukin(IL)-$1{\beta}$, IL-6, and interferon(IFN)-${\gamma}$, was detected by ELISA using a cytokine assay kit. After a 48-hr incubation with mitogens(ConA or lipopolysaccharide), mice splenocyte proliferation increased with the addition of a corn water extract supplement at 10, 50, 100, 250, 500, or $1,000\;{\mu}g/m\ell$. Production of IL-$1{\beta}$, IL-6, and IFN-${\gamma}$ increased in treatments supplemented with the corn water extract. In an in vitro study, splenocyte proliferation increased when $50\sim1,000\;{\mu}\ell/m\ell$ corn water extract was added. In an ex vivo experiment, the highest production of cytokines by activated peritoneal macrophages was observed in mice orally administered 500 mg/kg body weight/day.

• YAKHAK HOEJI
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• v.60 no.1
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• pp.21-28
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• 2016

Systemic lupus erythematosus (SLE) is characterized by dysregulatory production of proinflammatory cytokines and helper T (Th) cytokine-dependent autoantibody production. This study aims to investigate the protective effect of baicalin on the dysregulatory production of proinflammatory cytokines and Th cytokines in pristane-induced lupus mice. Mice were received i.p. a single injection of 0.5 ml of pristane, and then, later about 3 months, were used as a pristane-induced lupus model. The pristane-induced lupus mice were administrated orally with baicalin 50 mg/kg once in a day for 10 days. Immune cells obtained from the pristane-primed lupus control group (lupus control) and baicalin-treated pristaneprimed lupus mouse group (BAC lupus) were cultured for 24 h or 36 h with/without mitogens. These results demonstrated that LPS-induced production of macrophage and splenic TNF-${\alpha}$ and Con A-induced production of thymic IFN-${\gamma}$ were attenuated in BAC lupus compared to lupus control, while LPS-stimulated production of macrophage IL-10, Con A-stimulated production of splenic IL-10 and, $PGE_2$-reduced production of splenic IFN-${\gamma}$ enhanced. Therefore, these findings suggest that baicalin may protect from autoimmunity and disease activity in lupus via modulatory effect of proinflammatory cytokine overproduction and Th cytokine imbalance.