• Natural Product Sciences
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• v.11 no.2
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• pp.103-108
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• 2005

Bioflavone quercetin is thought to have an important role to inhibit bone loss by affecting osteoclastogenesis and regulating a number of systemic and local factors such as hormones and cytokines. In this study, we examined how quercetin acts on cytokine production and mineralization of osteoblast in the presence of tumor necrosis factor-alpha $(TNF-{\alpha})$ which has been known to play a pivotal role in bone metabolic diseases. Quercetin inhibited $TNF-{\alpha}-induced$ secretion of $IFN-{\gamma}$ and IL-6 in differentiated MC3T3-E1 cells. As indicated by the markers that are characteristics of the osteoblast phenotype, such as alkaline phosphatase (ALP) activity and calcium deposition, quercetin treatment slightly prevented the $TNF-{\alpha}-induced$ dramatic inhibition of differentiation and mineralization of MC3T3-E1 cells. Further, quercetin inhibited the production of nitric oxide induced by $TNF-{\alpha}$ in the cells. Collectively, our findings indicate that quercetin inhibites $TNF-{\alpha}-induced$ secretion of inflammatory cytokines in differentiated MC3T3-E1 cells without any cytotoxic effects.

• Korean Journal of Food Science and Technology
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• v.45 no.4
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• pp.508-514
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• 2013

2Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University Recently, we reported that diarylheptanoid hirsutenone (HST) effectively inactivated T lymphocytes. However, it has not been evaluated whether HST is involved in calcineurin or calmodulin inactivation. In the present study, cells were treated with T-cell inhibitors with or without HST. Our results revealed that HST successfully inhibited expression of T-helper type I (Th1) and Th2 cytokines. Co-treatment with HST and nuclear factor-activated T cell (NFAT) activation inhibitor III (INCA-6) showed a more sensitive effect than that with other inhibitors, suggesting that HST contributes to inhibition of dephosphorylation of NFAT in the cytosol. HST up-regulated cell cycle arrest genes and inhibited the growth of Staphylococcus aureus. These effects were confirmed in an NFAT electrophoretic-mobility shift assay via successful inhibition of NFAT translocation and in the histological recovery in a 2,4-dinitrochloro benzene-induced in vivo model. Taken together, HST was shown to effectively inhibit T-cell activation via inhibition of cytosolic NFAT dephosphorylation, similar to INCA-6.

• Korean Journal of Food Science and Technology
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• v.49 no.5
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• pp.559-566
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• 2017

This aim of this study was to examine the immunomodulatory activities of crude polysaccharides from Perilla frutescens Britton var. acuta Kudo (PCP) in mouse bone marrow-derived dendritic cells (BMDC) and splenocytes. The immunomodulatory activity was determined by cell viability, nitric oxide (NO) production, cell surface marker expression (CD 80/86 and MHC class I/II), and cytokine production in BMDC, and cell viability, and cytokine production in splenocytes. Cell proliferation and cytokine production (tumor necrosis factor; TNF-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and IL-12) tested in BMDC were significantly increased by PCP treatment. Additionally, the cell surface markers (CD 80/86, MHC class I/II) were highly increased by PCP treatment. For cytokine production in splenocytes, PCP treatment significantly increased the production of Th 1 cytokines [IL-2 and interferon (IFN)-${\gamma}$], but not Th 2 cytokines (IL-4). Therefore, PCP can induce immune cell activation and is a potential candidate for the development of nutraceuticals to boost the immune system.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.6
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• pp.776-784
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• 2014

Tuna cooking juice concentrate (TCJC) is by-produced during the canning processing of skipjack tuna Katsuwonus pelamis and it is well known that TCJC contains various nutritional components. Therefore, the immuno-stimulating activity of TCJC was investigated using macrophage RAW 264.7 cell line and the spleen cell isolated from BALB/c mice. The TCJC increased the production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ in a dose-dependent manner compared to the control in RAW 264.7 cells without any toxicity. In particular, the production of TNF-${\alpha}$ was increased over 300-fold. The production of both Th1 cytokine (such as IFN-${\gamma}$, TNF-${\alpha}$, IL-2, and IL-12) and Th2 cytokine (IL-4, IL-6, IL-10) was also increased by TCJC treatment in splenocytes. Moreover, the TCJC increased the splenocyte proliferation in a concentration-dependent manner compared to control. These results indicate that TCJC may enhance immune function by promoting various cytokine production.

• Korean Journal of Veterinary Research
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• v.41 no.2
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• pp.211-218
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• 2001

The $M_r$ 63,000 glycoprotein (GP63) and lipophosphoglycan (LPG) of Leishmania donovani were evaluated as vaccine candidates against visceral leishmaniasis. Mice were immunized with liposomeencapsulated GP63 and/or LPG that were purified from the soluble extract of L. donovani promastigotes, and were challenged with virulent amastigotes. Mice immunized with GP63/LPG in liposomes plus BCG resulted in a 27.4% reduction of amastigotes in the liver compared to the control group (liposomes plus BCG), and mice immunized with liposome-GP63 plus BCG failed to induce a protective immune response against the challenge infection. Immunization of mice with GP63 fused to the Schistosoma japonicum glutathione S-transferase (GP63-GST) plus BCG also failed to elicit protective immunity. To analyze the cause of failure to induce protection, cytokine release from the spleen cells of immunized mice and Leishmania-specific serum antibodies were analyzed. Spleen cells from mice immunized with GP63-GST plus BCG that were exposed to soluble extract of L. donovani in vitro produced 10-fold greater quantities of IFN-gamma and 3-fold greater quantities of IL-5 than cells from mice receiving BCG only or saline. Western blot analysis revealed that sera from these mice had Leishmania-specific antibodies recognizing 1 to 3 antigens of L. donovani with M. W. of 60-65 kDa. Although immunization of mice with GP63-GST induced a strong Th1 response, this study indicated that GP63-GST simultaneously elicited the Th2 response of the CD4+ T-cell, which was known to abrogate the protective immune response conferred by the Th1 effector function.

• IMMUNE NETWORK
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• v.11 no.1
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• pp.79-94
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• 2011

Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.1-13
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• 2017

Objective : Soybeans of Canavalia gladiata(CG) and root of Arctium lappa(AL) have been reported to have anti-inflammatory, antioxidant effect. However, the immunoregulatory mechanisms of its combinational prescription remain a matter of considerable debate. In the current study, we investigated whether CG and AL and its combinational prescription(CG+AL) regulate immune system using chronic immobilization-stress mouse model. Methods : C57BL/6J mice fixed for 2 hours into immobilization tube after CG, AL, CG+AL oral administration after 2 hours daily for 21 days. After every experiment has ended the C57BL/6J mice were sacrificed on 22 days. The production of Serotonin and Cortisol, lgA were observed by ELISA method, The proportion of immune cells such as T/B cell and macrophage, NK cell were measured by FACS. Then, Real-time PCR was performed to measure the mRNA expression of Inflammatory cytokines(IL-1beta, IL-6, TNF-a) and T cell activation cytokines(IL-2, IL-10, IFN-gamma, IL-12p35 / p40). Result : When chronic immobilization-stress mouse model were treated with CG+AL(1:4), the expression of mRNA were significantly decreased at the Inflammatory cytokines(IL-1beta, IL-6, TNF-a). While, the levels of mRNA were significantly increased at immune T cell activation cytokines. Additionally, CG+AL(1:4) combinational prescription group enhanced immune cells such as T/B cell and macrophage, NK cell. Furthermore, the Immuno-fluorescence result of brain tissue can confirm that CG+AL(1:4) group significantly increased the BDNF expression. Conclusion : These result suggest that CG+AL(1:4) combinational prescription has Immune System enhancement via stress-mediated immunocyte.

• Journal of Haehwa Medicine
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• v.18 no.1
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• pp.29-41
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• 2009

Wished to examine closely effect that SoPungDoJeokTang-KaMi (SPDJTK) medicines used to atopy dermatitis disease patient get in atopy eruption control experimentally. SPDJTK medicines controlled $CD4^+/IFN-\gamma$, and $CD4^+/CD25^+/foxp3^+$ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates T cells of a NC/Nga mouse same time by anti-CD40/rmIL-4, and interleukin-$1{\beta}$, IL-6, TNF-$\alpha$, and TGF-$\beta$ mRNA outturn that bear in T and B cells decreased remarkably by SPDJTK medicines. Intracellular staining of splenocytes anti-CD40/rmIL-4 plus rmIL-4 stimulated as described in a, assessed after 24 h, SPDJTK exerts a mainly immunosuppressive effect that acts at least partially through suppression of the transcription factor GATA3 expression in $CD4^+$ T cells. Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen specially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Result that Th1 cell and Th2 cell observe to be shifted by cytokine expression with $CD4^+/CD25^+/foxp3^+$ Treg cells induction by SPDJTK medicines could know that SPDJTK medicines can use usefully in allergy autoimmnune diease.

• Journal of Haehwa Medicine
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• v.16 no.2
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• pp.147-169
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• 2007

To evaluate the therapeutic effects of BGG on atopic dermatitis, we investigated the composition of immune cells of lymph node, PBMC and skin of Dermatophagoides farinae-induced NC/Nga mice. The levels of immunoglobulins in serum were analyzed at the protein level and the amount of pathologic cytokines were investigated using CD3/CD28 stimulated splenocytes. The results are summarized below; 1. BGG showed no cytotoxic effect up to $200\;{\mu}g/m{\ell}$ on mLFC in vitro. 2. BGG showed no hepatotoxicity in vivo based on the levels of ALT and AST. 3. Atopic dermatitis was improved through naked eye examination. BGG reduced the skin clinical index from 2.9 to 1.3 (p<0.01). 4. H&E and toluidine blue staining of tissue biopsies revealed that BGG inhibited the infiltration of lymphocytes and mast cells to skin. 5. BGG reduced the number of CD19 positive B cells in PBMCs by 16% (p<0.01), whereas cells were increased by 26% (p<0.05) in lymph nodes. 6. BGG reduced the numbers of B220+/CD23+ cells by 15% (p<0.01) and 33% in PBMCs and lymph node, respectively. 7. BGG reduced the numbers of B220+/IgE+ cells in PBMCs and lymph node by 21% and 33% (p<0.01), respectively. 8. BGG suppressed the levels of IgE (13%, p<0.001) as well as IgM (34%, p<0.001), IgG2a (40%, p<0.001) and IgG2b (26%, p<0.05). 9. BGG reduced the levels of IL-4 and IFN-$\gamma$ by 7% (p<0.05) and 13% (p<0.001) in anti-CD3 and anti-CD28-activated splenocytes, respectively. 10. BGG considerably inhibited the production of TNF-$\alpha$ and IL-6 by 42% (p<0.01) and 15% in the serum, respectively. Based on the results above, we concluded that BGG has therapeutic effects on atopic dermatitis by regulating the differentiation of B cells and isotype switching of IgE. Further investigations on the molecular mechanisms of BGG on atopic dermatitis are anticipated.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.982-991
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• 2007

The present study was done to assess the suppressive effects of Haedongpi-san(HDPS), a traditional herbal medicine, on collagen induced arthritis (CIA) in mice and to examined it's effects on immune system. Oral administration of HDPS (200 or 400 mg/Kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 30 mg/Kg), a positive control. Histological examinations reveled that HDPS inhibited infiltration of inflammatory cells into affected paw joint, and bone erosion and cartilage destruction were greatly reduced compared with control. In paw joint, the number of CD3+ cells and CD11b+/Gr-1+ cells were greatly reduced by HDPS. The levels of pathologic cytokines including TNF-a and IL-6 were significantly decreased in the serum by oral treatment with HDPS. The levels of $IFN-{\gamma}$ in the culture supernatant of splenocyte stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. Rheumatoid factors including IgG, IgM and collagen specific antibody were present much lower in the serum of HDPS treated mice than control. In peripheral blood mononuclear cells of HDPS treated mice, the percentage of CD3+, CD3+/CD69+, CD4+, CD4+/CD25+ cells were significantly decreased, while CD19+ cells were slightly increased compared with control. The absolute number of CD19+, CD3+, CD3+/CD69+, CD4+/CD25+, CD49b+ cell in spleen from HDPS treated mice were significantly decreased. The absolute number of CD3+, CD3+/CD69+, CD4+, CD4+/CD25+ CD8+, CD49b+, CD3+/CD49b+ cells in draining lymph node were significantly increased compared with control. Taken together, HDPS has suppressive effects on rheumatoid arthritis by modulating immune system, and has potential to use as an therapeutic for rheumatoid arthritis.