• Journal of Acupuncture Research
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• v.22 no.3
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• pp.185-200
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• 2005

Objective : The aim of this study was to investigate the asthma-suppressive and immune-regulatory effect of AHCR-HA(ASARI HERBA CUM RADICE Herbal-acupuncture) at Pyesu(BLl3) on OVA(ovalbumin)-induced asthma in mice. Methods : C57BL/6 mice out of all the experimental groups, except the Normal group and the AHCR-HA group, were sensitized and challenged with OVA The mice in the AHCR-HA group and the OVA-AHCR-HA group were treated with AHCR-HA(1%) at Pyesu(BL13). The mice in the OVA-Saline group were injected with saline at Pyesu(BL13). The mice in the OVA-Needle-Prick group were treated with a single prick with an injection needle at Pyesu(BL13). AHCR-HA saline injection and needle prick were administered for 8 weeks, three times a week. Result : 1. The populations of granulocytes, CD3e-/CCR3+ cells, CD69+/CD3e+ cells, CD4+ cells and CD23+/B220+ cells in the OVA-induced asthmatic mouse lungs decreased significantly by AHCR-HA. 2. The lung weight, total cells in lung, total leukocytes in BALF, eosinophils in BALF, collagen accumulation in the lung sections of the OVA-AHCR-HA group decreased significantly. 3.The concentrations of IL-4, IL-5, IL-13, IgE in BALF and serum of the OVA-AHCR-HA group decreased significantly. 4. The numbers of Gr-1+/CD11b+, CCR3+, CD3e+, CD19+, CD3e+/CD69+cells in the OVA-AHCR-HA group decreased significantly. 5. The mRAN expressions of $TNF-{\alpha}$, IL-5, IL-4 and IL-13 in lung of the OVA-AHCR-HA group decreased significantly. 6. The AHCR-HA group didn't show any considerable difference from the Normal group. The OVA-saline group and the OVA-Needle prick group showed suppressive effects on OVA-induced asthma however they were not statistically significant. Conclusion : These results suggest that AHCR-HA at Pyesu(BL13) is considered to be effective in treating asthma and to be put to practical use in the future asthma clinic.

• Korean Journal of Medicinal Crop Science
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• v.26 no.1
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• pp.8-18
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• 2018

Background: This present study was conducted to evaluate the anti-inflammatory and immune regulatory effects of Aucklandia lappa Decne (AL). Methods and Results: We measured cytotoxicity, nitric oxide (NO) content, mRNA expression (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$), protein expression (iNOS, COX-2, and $I{\kappa}B$) and phagocytic activity in RAW264.7 cells. Male BALB/c mice were fed 100 mg/kg AL (Aucklandia lappa Decneon 70% ethanol extract) and 250 mg/kg AL for 4 weeks; thereafter, we observed B/T or $CD4^+/CD8^+$ lymphocyte subpopulation change, and expression patterns of $CD4^+$ and $CD8^+$ lymphocytes by immunohistochemical staining in mouse splenocytes and/or thymocytes. To determine the experimental concentration of AL, cell viability was measured by MTT assay and tested at $12.5{\mu}g/m{\ell}$ or less. AL inhibited the levels of NO, lymphokine production (IL-$1{\beta}$, and TNF-${\alpha}$), and mRNA (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$) and protein (iNOS, and COX-2) expression. Additionally, the levels of $I{\kappa}B$, phagocytic activity, and splenic and thymic T lymphocytes, especially $T_H$ and $T_C$ cells were significantly increased in AL administered mice. The immuno-reactive density of $CD4^+$ and $CD8^+$ lymphocytes was stronger in AL groups than in the normal group. AL stimulated NO, iNOS, and COX-2, and regulated IL-1${\alpha}$, IL-$1{\beta}$, TNF-${\alpha}$, and $I{\kappa}B$ in macrophages treated with LPS (lipopolysaccharide). In addition, AL increased the phagocytic activity of macrophages and the immunity of mouse T ($T_H$, and $T_C$) cells. Conclusions: These results suggested that AL might show anti-inflammatory activity via the suppression of various inflammatory markers and immuno-regulatory activity.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.304-312
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• 2018

Regulatory T cells (Treg), known as immune-suppressors, may help modulate the immune response. In this study, we investigated the effect of Treg-derived $TGF-{\beta}1$ on pancreatic islet cell function in vitro and in vivo. One hundred eighty IEQ (islet equivalents) of pancreatic islets, the marginal amount to regulate blood glucose level after syngeneic islet transplantation in mouse type 1 diabetes (T1D) model, were co-cultured with $4{\times}10^6$ Treg cells for 48 hours. The changes in $TGF-{\beta}1$, interleukin-6 (IL-6), and insulin secretion levels were measured and analyzed among the Treg-only group, the islet-only group, and the Treg/islet co-cultured group. In the Treg/islet co-cultured group, IL-6 and insulin secretion levels were increased (P<0.0005, P<0.005) and islet viability was improved (P<0.005) compared with the islet-only group. Furthermore, after transplantation, the co-cultured islets regulated blood glucose levels efficiently in the T1D mouse model. These data suggest that Treg could improve islet functions and viability via the $TGF-{\beta}1$ secretion pathway (P<0.05~0.005), thus the use of Treg in islet transplantation should be explored further.

• Parasites, Hosts and Diseases
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• v.54 no.2
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• pp.163-171
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• 2016

As most infections by the helminth parasite elicit the recruitment of $CD4^+CD25^+Foxp3^+$ T ($T_{reg}$) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated $T_{reg}$ cells, we compared the expression levels of $T_{reg}$ cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of $T_{reg}$ cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated $T_{reg}$ cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of $T_{reg}$ cells in the muscle tissue.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.3 no.1
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• pp.67-84
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• 1997

Bujeonghangamtang(扶正抗癌湯) has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Bujeonghangamtang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene. (MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(Sl80 cells). Treatment of the Bujeonghangamtang water-extract (dailly 1mg／mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Bujeonghangamtang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice (TBM). Bujeonghangamtang also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size, and some developed tumors were regressed by the continuous treatment of Bujeonghangamtang extract into TBM. In vitro, treatment of Bujeonghangamtang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Bujeonghangamtang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Bujeonghangamtang-administration to mice enhanced NK cells activities. These results demonstrated that Bujeonghangamtang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Bujeonghangamtang might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.234-250
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• 1998

Bujeonghangamtang(扶正抗癌湯) has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carroed out to evaluate the possible therapeutic or antitumoral effects of Bujeonghangamtang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by .the typical application of 3-methylcholanthrene (MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(Sl80 cells). Treatment of the Bujeonghangamtang water-extract (dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Bujeonghangamtang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice (TBM). Bujeongmngamtang also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurence-frequency and their size, and some developed tumors were regressed by the continuous treatment of Bujeonghangamtang extract into TBM. In vitro, treatment of Bujeonghangamtang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Bujeonghangamtang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Bujeonghangamtang-administration to mice enhanced NK cells attivities. These results demonstrated that Bujeonghangamtang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Bujeonghangamtang might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.519-526
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• 2023

Present study explored immunostimulatory effects of Astragalus membranaceus and Zanthoxylum schinifolium 1:1 (w:w) mixture (AZM-1:1) in Raw264.7 cells, mouse macrophage derived cells. Treatment with 100-400 ㎍/mL of AZM-1:1 in Raw264.7 cells significantly increased nitric oxide production in parallel with inducible nitric oxide synthase mRNA expression without affecting cytotoxicity. In addition, AZM-1:1 dose-dependently increased prostaglandin E₂ production in conditioned medium along with cyclooxygenase-2 mRNA induction. Moreover, AZM-1:1 induces the transcription of tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1. Immunoblot analyses revealed that AZM-1:1 significantly increased the phosphorylation of mitogen-activated protein kinases, provoked phosphorylation-mediated degradation of inhibitory-κBα, and phosphorylated p65. Furthermore, treatment with AZM-1:1 promoted phagocytosis of Escherichia coli particle labeled with green fluorescence. Taken together, AZM-1:1 may be a promising nutraceutical for stimulation the innate immune system, including macrophages.

• 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.

• Journal of Acupuncture Research
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• v.22 no.1
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• pp.131-144
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• 2005

Objective : The aim of this study is to observe the effect of Herbal-acupuncture(HA) with Luffae Fructus Retinervus Herbal-Acupuncture Solution(LFR-HAS) at ST36(Joksamni) on Collagen Ⅱ -induced arthritis(CIA) in mice. Methods : DBA1/J mice were immunized with bovine type Ⅱ collagen(CⅡ) on days 0 and 21 to induce an arthritis. The mice were divided into 5 groups. They were Normal group(wild type), Control group(CIA), Saline group(CIA +saline injection), Needle Prick group(CIA +single Prick with an injection needle) and LFR-HA group(CIA +LFR-HA treatment). The saline injection, needle prick and LFR-HA were made on the right ST36(Joksamni) of mice for 5 weeks, 3 times a week beginning 4 weeks after the booster immunization. Results : 1. The highest synovial rate of lung fibroblasts was measured in the 1% LFR-HAS. 2. TNF-${\alpha}$ expression of survival cells from CIA mouse joint was significantly reduced in the 1% LFR-HAS. 3. The incidence of arthritis and the spleen weight of CIA mouse were significantly reduced by the Luffae Fructus Retinervus Herbal-Acupuncture (LFR-HA) at ST36. 4. The concentrations of IL-6, INF-${\alpha}$, INF-${\alpha}$, IgG, IgM, and anti-collagen Ⅱ in the CIA mouse serum were significantly reduced by the LFR-HA at ST36. 5. The histological examination showed that, in the LFR-HA group, the cartilage destruction and the synoviocyte proliferation in the CIA mouse joint were not significant compared to the control group, and the collagen fiber was similarly expressed as the normal group. 6. In the LFR-HA group, the ratio of CD3e+ to CD19+ cell, and the ratio of CD4+ to CD8+ cell in the lymph node were similarly maintained as those of the normal group. 7. CD69+/CD3e+ and CD11a+/CD19+ cells in the CIA mouse lymph node were significantly reduced by the LFR-HA at ST36. 8. CD11b+/Gr-1+ cells in the CIA mouse joint were significantly reduced by the LFR-HA at ST36. Conclusions : These results indicate that Luffae Fructus Retinervus Herbal-Acupuncture (LFR-HA) at ST36 may regulate the immune system and have a therapeutic effect on Collagen-induced arthritis(CIA) in mice.

• IMMUNE NETWORK
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• v.4 no.4
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• pp.216-223
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• 2004

Background: It is well known that IgA isotype switching is induced by $TGF-{\beta}1$. LPS-activated mouse normal B cells well differentiate into IgA secreting plasma cells under the influence of $TGF-{\beta}1$. Nevertheless, there are lots of difficulties in studying normal B cells in detail because it is not simple to obtain highly purified B cells, showing low reproducibility and transfection efficacy, moreover impossible to keep continuous culture. To overcome these obstacles, it is desperately needed to develop B cell line which acts like normal B cells. In the present study, we investigated whether CH12F3-2A lymphoma cells are appropriate for studying IgA isotype switching event. Methods: CH12F3-2A B cell line was treated with LPS and $TGF-{\beta}1$, then levels of germ-line (GL) transcripts were measured by RT-PCR, and $GL{\alpha}$ promoter activity was measured by luciferase assay. In addition, membrane IgA (mIgA) expression and IgA secretion were determined by FACS and ELISA, respectively. Results: $TGF-{\beta}1$, regardless of the presence of LPS, increased level of $GL{\alpha}$ transcripts but not $GL{\gamma}2b$ transcripts. However, IgA secretion was increased dramatically by co-stimulation of LPS and $TGF-{\beta}1$. Both mIgA and IgA secretion in the presence of $TGF-{\beta}1$ were further increased by over-expression of Smad3/4. Finally, $GL{\alpha}$ promoter activity was increased by $TGF-{\beta}1$. Conclusion: CH12F3-2A cell line acts quite similarly to the normal B cells which have been previously reported regarding IgA expression. Thus, CH12F3-2A lymphoma cell line appears to be adequate for the investigation of the mechanism(s) of IgA isotype switching at the cellular and molecular levels.