• Title/Summary/Keyword: IFN-$\gamma$

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Priming of Autoreactive $CD8^+T$ Cells Is Inhibited by Immunogenic Peptides Which Are Competitive for Major Histocompatibility Complex Class I Binding

  • You, Sooseong;Choi, Yoon Seok;Hong, Seokchan;Shin, Eui-Cheol
    • IMMUNE NETWORK
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    • v.13 no.3
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    • pp.86-93
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    • 2013
  • In the present study, we investigated if priming of autoreactive $CD8^+T$ cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of $K^b$-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for $K^b$ binding inhibited IFN-${\gamma}$production and proliferation of TRP2-180-specific $CD8^+T$ cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific $CD8^+T$ cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive $CD8^+T$ cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific $CD8^+T$ cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.

Ginseng radix induces apoptosis in HL-60 cells and its mechanism as little relation with TNF-α production

  • Koo, Hyun-Na;Shin, Soon-Shik;Park, Jin-Han;Kim, Na-Hyung;Hong, Seung-Heon;Kim, Hyung-Min
    • Advances in Traditional Medicine
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    • v.4 no.3
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    • pp.171-178
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    • 2004
  • Ginseng radix, the root of Panax ginseng C. A. Meyer (Araliaceae), is a medicinal plant used world-widely and has been reported to have various biological effects. To investigate the effects of Ginseng radix on HL-60 cell apoptosis, MTT assay, DNA fragmentation assay and flow cytometry were performed on HL-60 cells. Cells were treated with Ginseng radix at different concentrations $(10^{-4},\;10^{-3}\;and\;10^{-2};\;dilution\;rate)$. Ginseng radix significantly induced cells apoptosis with a time- and dose-dependent manner. To determine whether Ginseng radix-induced apoptosis is due to increase of tumor necrosis factor $(TNF-{\alpha})$ secretion, enzyme-linked immunosorbent assay was performed on HL-60 cells. Unexpectedly, Ginseng radix $(96\;{\pm}\;5\;pg/ml)$ significantly decreased the $TNF-{\alpha}$ secretion compared with control $(174\;{\pm}\;14\;pg/ml)$. Furthermore, Ginseng radix with $rIFN-{\gamma}$ synergistically increased nitric oxide production in mouse peritoneal macrophages. Taken together, our data indicate that Ginseng radix induce apoptosis on HL-60 cells without increase of $TNF-{\alpha}$ secretion and could be used for a supplementary remedy of cancer.

Immune Stimulating Efficacy of Soluble β-1,3-glucans (수용성 β-1,3-glucans의 면역 활성 효능에 대한 연구)

  • Shim, Jung-Hyun;Choi, Won-A;Kim, Jong-Wan;Lee, Hae-Sook;Baek, Tae-Woong;Cho, Min-Cheol;Lee, Kyung-Ae;Sang, Byung-Chan;Yoon, Do-Young
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.156-163
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    • 2003
  • Background: $\beta$-1,3-glucans are well known to enhance the immune reactions, resulting in antitumor, antibacterial, antiviral, anticoagulatory and wound healing activities. $\beta$-1, 3-glucans have various activities depending on molecular weight, degree of branching, conformation, water-solubility and intermolecular association. However, the $\beta$-1,3-glucan linked backbone structure is essential and $\beta$-D-glucopyranosyl units are required for immuno-potentiating activities. Result: In this study, we tested the immunophamacological activities of soluble $\beta$-1,3-glucans and confirmed the following activities: (1) $IFN-{\gamma}$ production in PBMCs in the presence or the absence of PHA, LPS, or IL-18; (2) induction of various cytokines in the spleen and thymus; (3) adjuvant effect on the antibody production; (4) nitrogen oxide synthesis in macrophages; (5) the cytotoxic and antitumor effects on cell lines and ICR mice. Conclusion: These results strongly suggested that $\beta$-1,3-glucans possessed various immuno-pharmacological activities.

Influence of Immunity Induced at Priming Step on Mucosal Immunization of Heterologous Prime-Boost Regimens

  • Eo, Seong-Kug
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.110-117
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    • 2003
  • Background: The usefulness of DNA vaccine at priming step of heterologous prime-boost vaccination led to DNA vaccine closer to practical reality. DNA vaccine priming followed by recombinant viral vector boosting via systemic route induces optimal systemic immunity but no mucosal immunity. Mucosal vaccination of the reversed protocol (recombinant viral vector priming-DNA vaccine boosting), however, can induce both maximal mucosal and systemic immunity. Here, we tried to address the reason why the mucosal protocol of prime-boost vaccination differs from that of systemic vaccination. Methods: To address the importance of primary immunity induced at priming step, mice were primed with different doses of DNA vaccine or coadministration of DNA vaccine plus mucosal adjuvant, and immunity including serum IgG and mucosal IgA was then determined following boosting with recombinant viral vector. Next, to assess influence of humoral pre-existing immunity on boosting $CD8^+$ T cell-mediated immunity, $CD8^+$ T cell-mediated immunity in B cell-deficient (${\mu}K/O$) mice immunized with prime-boost regimens was evaluated by CTL assay and $IFN-{\gamma}$-producing cells. Results: Immunity primed with recombinant viral vector was effectively boosted with DNA vaccine even 60 days later. In particular, animals primed by increasing doses of DNA vaccine or incorporating an adjuvant at priming step and boosted by recombinant viral vector elicited comparable responses to recombinant viral vector primed-DNA vaccine boosted group. Humoral pre-existing immunity was also unlikely to interfere the boosting effect of $CD8^+$ T cell-mediated immunity by recombinant viral vector. Conclusion: This report provides the important point that optimally primed responses should be considered in mucosal immunization of heterologous prime-boost regimens for inducing the effective boosting at both mucosal and systemic sites.

Inhibitory effect of mushrooms extract on TNF-α/INF-γ induced-cytokine in human keratinocytes, HaCaT (버섯류 추출물의 피부각질세포(HaCaTcell) 내 염증성 사이토카인 억제효과)

  • Choi, Eun-Ju;Kim, Eun-Kyung;Ji, Yong-Seok;Lee, Chang-Jin
    • Journal of Mushroom
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    • v.13 no.3
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    • pp.170-174
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    • 2015
  • Mushroom is known for anti-inflammatory and anti-oxidative potential. This study provides evidence that the inhibitory effect of mushroom on the expression of pro-inflammatory cytokines in human keratinocytes, HaCaT cells. To define the underlying mechanisms of action, tumor necrosis factor${\alpha}$/$IFN{\gamma}$-activated human keratinocytes model was used. Mushroom significantly inhibited the expression of cytokines in HaCaT cells. Taken together, the results demonstrate that mushroom inhibited inflammtion, suggesting that mushroom (DW extract: Grifola frondosa Cordyceps militaris), (Ethanol extract: Ganoderma lucidum, Lentinus edodes, Cordyceps militaris, Flammulina velutipes) might be a candidate for the treatment of skin inflammation.

The Effects of Lycium chinese Mill., Morus alba L. and Their Combination on the Asthmatic Murine Model (천식동물모델을 이용한 지골피(地骨皮), 상백피(桑白皮) 및 두 배합약물의 실험적 연구)

  • Seo, Chang-Woo;Lee, Young Cheol;Lee, Jang-Cheon
    • Herbal Formula Science
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    • v.21 no.1
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    • pp.36-50
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    • 2013
  • Objectives : To clarify the possible effect of Lycium chinese Mill (LC)., Morus alba L (MA)., and Lycium chinese Mill. +Morus alba L. (LC+MA), we have examined their influence on the development of pulmonary eosinophilic inflammation in the asthmatic murine model. Methods : Female Balb/c mice (5weeks) were immunized on two different days (21 days and 7 days before inhalational exposure) by intraperitonial injections of 0.2ml alum-precipitated Ag containing $100{\mu}g$ of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 minutes/day on 3 days/week for 8 weeks (at a flow rate of 250 L/min, 2.5% ovalbumin in normal saline) and, LC, MA, and LC+MA (500 mg/kg) were orally administered 3 times per a week for 8 weeks. Results : The suppressive effect of LC, MA, and LC+MA were demonstrated by the accumulation of eosinophills into airways, with the reduction of eosinophil, total lung leukocytes numbers. These were correlated with the marked reduction of IL-5, IL-13 and IL-4 levels in the BALF and serum. OVA-specific IgE levels were also decreased in serum and BAL from these mice. LC, MA, and LC+MA decreased eosinophil CCR3 expression and CD11b expression in lung cells. Conclusions : These results indicate that LC, MA, and LC+MA have high inhibitory effects on airway inflammation and hyper-responsiveness in the asthmatic murine model. The suppression of IL-5, IgE, eosinophil CCR3 expression and CD11b expression, and the increase of IFN-${\gamma}$ production in BALF seem to contribute to this effect. Hence, the results indicated that LC, MA, and LC+MA could act as a immuno-modulator which possesses anti-inflammatory and anti-asthmatic property by modulating the imbalance between Th1 and Th2 cytokines.

Broussonetia kazinoki Siebold stimulates immune response in ovalbumin-immunized mice

  • Jung, Da-Young;Ha, Hye-Kyung;Lee, Ho-Young;Lee, Jin-Ah;Jeong, Seung-Il;Choi, Young-Jae;Shin, Hyeun-Kyoo
    • The Journal of Korean Medicine
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    • v.32 no.3
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    • pp.10-17
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    • 2011
  • Objective: To evaluate the immune-stimulatory potential of extracts of Broussonetia kazinoki Siebold (BK) on specific cellular and humoral immune responses in ovalbumin (OVA)-immunized mice. Material and Methods: C57BL/6 mice were immunized intraperitoneally with OVA/alum ($100{\mu}g/200{\mu}g$) on days 1, 8, and 15. BK (100, 300 or 1000 mg/kg) was given to mice orally for 21 days (from day 1 to day 21). At day 22, OVA-, lipopolysaccharide (LPS)- and concanavalin A (Con A)-stimulated splenocyte proliferation and OVA-specific and total antibodies were measured in plasma. Further, the effects of BK on expression of cytokine mRNA in OVA-immunized mice splenocytes were evaluated by RT-PCR analysis. Results: BK significantly enhanced OVA-, LPS-, and Con A-induced splenocyte proliferation in OVA-immunized mice (p<0.01). BK also significantly enhanced total IgM and OVA-specific IgG1 levels in plasma compared with the OVA control group. Moreover, BK up-regulated significantly the expression of mRNA level of IL-2 and IFN-${\gamma}$ in splenocytes. Conclusions: BK has immune-stimulating activity in an OVA-immunized mouse model system, enhancing the Th1 immune response. BK showed no cytotoxicity in this system, suggesting that BK may be a safe and effective adjuvant in humans.

Regulatory Effects of Allergic Bronchial Asthma Responses by KagamJwaGwiEum (가감좌귀음(加減左歸飮)의 알레르기성 기관지천식(氣管支喘息) 반응(反應) 조절(調節) 효과(效果))

  • Park, Eun-Jung;Lee, Hai-Ja;Park, Jong-Ik;Park, Young-Joo
    • The Journal of Pediatrics of Korean Medicine
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    • v.18 no.2
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    • pp.31-48
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    • 2004
  • Objective : KagamJwagwiEum(KJE) has been used for the purpose of prevention and treatment of bronchial asthma and allergic asthma in Korea. To investigate the biological effect of KJE, the author examined cytotoxicity and inflammatory cytokines secretion with human leukemic mast cell line, HMC-1. Methods: HMC-1 was stimulated with phorbol 12-myristate 13-acetate(PMA) and calcium ionophore A23187. KJE by itself had no effect on viability of HMC-l. The effects of KJE on the secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$, interleukin(IL)-6 and IL-8 from HMC-1 were evaluated with enzyme-linked immunosorbent assay. Results : KJE inhibited PMA plus A23187-induced $TNF-{\alpha}$ and IL-6 secretion. But KJE had no effect IL-8 secretion: KJE had immunoregulatory effects on cytokines, increased secretion of NO and $TNF-{\alpha}$ but did not effect IL-12 secretion when the cells were primed and trigged with $IFN-{\gamma}$ in the peritoneal macrophages of C57BL/6 mice. Conclusions : Taken together, these results suggest that KJE inhibit the production of inflammatory cytokines in HMC-1 cells and activate macrophages.

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Effect of Korean Red Ginseng on Artificial Sand Dust (ASD) Induced Allergic Lung Inflammation

  • Kim, Jung-Ha;Lee, Tae-Jin;Im, Jee-Aee;Lee, Duk-Chul
    • Biomedical Science Letters
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    • v.20 no.3
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    • pp.173-179
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    • 2014
  • Asian sand dust is known to promote various respiratory symptoms or disorders. For the prevention of harmful health effects by Asian sand dust, the best strategy is known to avoid or reduce exposure to the Asian sand dust. Several studies have shown that Korean red ginseng (RG) has anti-inflammatory and anti-allergic effects. The study aimed to clarify the effect of Korean red ginseng intake on lung inflammation responses to artificial sand dust (ASD) similar to Asian sand dust. BALB/c mice were divided into five groups (n=12) of control (saline), ovalbumin (OVA), OVA with ASD, OVA plus RG with ASD, and OVA plus dexamethasone (DEXA) with ASD. Histopathologic evaluation of lung was conducted. Interleukin (IL)-5, IL-12, interferon (IFN)-${\gamma}$, IL-13, monocyte chemotactic protein (MCP)-1, and eotaxin within bronchoalveolar lavage (BAL) fluid were measured by ELISA. OVA+ASD group significantly increased concentrations of IL-5, IL-13, MCP-1, and eotaxin (P<0.01) compared to the control. OVA+ASD+RG group showed significant decreased levels of IL-2, IL-13, MCP-1 and eotaxin (P<0.01) compared with OVA+ASD. Between RG and DEXA treatment groups, there was no significant difference in all cytokines and chemokines. The inflammatory cells were significantly decreased in treatment groups with RG or DEXA compared to OVA+ASD group. This study suggests a beneficial effect of Korean RG administration in preventing inflammation of lung resulting from Asian sand dust.

Studies of the Anti-cancer Effects of Bistortae Rhizoma (권삼(拳蔘)의 항암효과에 대한 연구)

  • Kim, June-Beom;Han, Hyo-Sang;Lee, Young-Jong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.5
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    • pp.1139-1144
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    • 2009
  • This study was purposed to research the anti-cancer effects of Bistortae Rhizoma. A total extract of Bistortae Rhizoma decoction was prepared. By measuring the cell proliferation, apoptosis, morphology and cytokine level from the extracts, the influence on HepG2 cell, SNU-1 cell and A549 cell was compared. The Bistortae Rhizoma decoction extract did not control HepG2 cell proliferation but controlled SNU-1 cell and A549 cell proliferation. In particular, the inhibitory effect on SNU-1 cell proliferation was highest. The Bistortae Rhizoma decoction extract showed to increase the apoptosis of the HepG2 ceil, SNU-1 cell and A549 cell in a dose-dependent manner. In particular, the promotion effect of the apoptosis was highest in SNU-1 cell. Among the various fraction extracts of the Bistortae Rhizoma decoction, n-BuOH extraction showed the greatest increase of the apoptosis of the HepG2 cell. The Bistortae Rhizoma decoction extract decreased dose-dependently the secretion of the TGF-$\beta$ in the HepG2 cell, SNU-1 cell and A549 cell and increased the secretion of the TNF-$\alpha$ and the IFN-$\gamma$. These results suggest that the total extract of Bistortae Rhizoma decoction has anti-cancer effect against SNU-1 cell and A549 cell.