• Journal of Acupuncture Research
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• v.18 no.4
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• pp.125-142
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• 2001

Objective : The purpose of this study is to observe the effect of Aqua-acupuncture with Stephania Tetrandra Solution (ST-AS) on arthritis. Methods : The author performde several experimental items : that isgene expression and secretion of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, MMP-2, production of ROS, paw thickness, DTH, weight of spleen, expression of CD4+, CD8+, CD19+ in the spleen, production of IL-6, TNF-${\alpha}$, examination of histology. Results : The obstain results are summarized as follows. 1. IL-$1{\beta}$, IL-6, TNF-${\alpha}$ gene expression of hFLS were significantly inhibited in treatmentgroup, and gene expression of MMP-2 was not inhibited in treatmentgroup. 2. The secretion amount of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ were significantly inhibited in treatmentgroup. 3. Expression of P-38 MAP kinase and production of ROS were inhibited in treatmentgroup. 4. Treatmentgroup were significantly inhibited the incidence of arthritis, hind paw edema, the index of arthritis and DTH of CIA (collagen II-induced arthritis) mice. 5. Treatmentgroup were significantly decreased splenetic weight and the number of CD4+, CD8+, CD19+ activated cells and secretion aroout of IL-6, TNF-${\alpha}$ of CIA (collagen II-induced arthritis) mice.. 6. Treatmentgroup were expressed form of new bone, synoviumin, new margine in histology imperison to controlgroup. Conclusions : Taking all these observations into account, ST-AS injection is considered to be effective in treating arthritis and put to practical use in future arthritis clinic.

• Natural Product Sciences
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• v.13 no.2
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• pp.123-127
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• 2007

We investigated effect of small black soybean fraction (SBSF) T cell-mediated responses for tumor surveillance and proliferation in leukemia cells in vitro. Each SBSF butanol fraction (SBSFBu) and SBSF chloroform fraction (SBSFCh) was administered p.o. once a day far 21 days in BALB/c mice and then levels of serum cytokines and subpopulation of lymphocytes were measured. Moreover, SBSF fraction was treated into the cultured various cell lines for proliferation in leukemia cell lines, NO production by RAW264.7 cells, and expression of p53 gene in U937 leukemia cells. These results showed that SBSFBu increased levels of serum IL-4but not IL-2 and IFN-${\gamma}$, and increased expression of CD4$^+$ T cells and CD8$^+$ T cells in splenocytes in vivo, while SBSFCh increased levels of serum IL-2 and IFN-${\gamma}$ but decreased IL-4, and increased CD8$^+$ T cells but not CD4$^+$ T cells. Moreover, both of SBSFBu and SBSFCh inhibited proliferation of HL60, U937, and L1210 leukemia cell lines in a dose-dependent manner, up-regulated NO production by RAW264.7 cells in a dose-dependent manner, and enhanced expression of p53 gene in U937 leukemia cells. Our findings indicate that SBSFBu and SBSFCh may enhance T cell-dependent immune responses, and that both of SBSFBu and SBSFCh may inhibit proliferation of leukemia cells by up-regulation of NO production and expression of p53 gene.

• The Journal of Pediatrics of Korean Medicine
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• v.29 no.4
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• pp.39-66
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• 2015

Objectives The purpose of this study is to investigate the effects of Sesamum indicum extracted (SEI) on atopic dermatitis in an in-vitro and in-vivo experiment using a MC/9 murine mast cells and a NC/Nga mouse. Methods In-vitro experiment, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF mRNA expression were evaluated by Real-time PCR, IL-13, MIP-$1{\alpha}$ production by ELISA and manifestations of NFAT-1, NFAT-2, c-jun, c-fos, NF-${\kappa}B$ p65 transcription factors by western blotting. In-vivo experiment, we measured WBC, Eosinophil, Neutrophil, and serum IL-5, IL-13 in NC/Nga atopic dermatitis mouse, IL-5, IL-13, IFN-${\gamma}$, IL-4 in the spleenocyte culture supernatant by ELISA, the absolute cell numbers of CD4+, CD8+, +Gr-1+CD11b, B220+CD23+ in the axillary lymph node (ALN), peripheral blood mononuclear cells (PBMCs) and dorsal skin tissue, IL-5, IL-13 by Real-time PCR, the distribution of tissue inflammation and cellular infiltration by H&E and toluidine blue. Results SEI decreased IL-4, IL-5, IL-6, IL-13, GM-CSF, TNF-${\alpha}$ mRNA expression, IL-13, MIP-$1{\alpha}$ production and the expression of transcription factors including NFAT-1, c-jun, NF-${\kappa}B$ p65 in MC/9 murine mast cells. SEI orally administration decreased cell number of WBC, Eosinophil, the level of serum IgE, total cell number of ALN and dorsal skin tissue, absolute cell number of CD4+, CD8+, B220+CD23+ in the ALN. SEI orally administration also increased absolute cell number of CD8+/CD3+ and decreased Gr-1+/CD11b+ in PBMCs, decreased CD4+ in dorsal skin tissue, inhibited IL-5, IL-13 mRNA expression. Infiltration levels of inflammatory immune cells, mast cells and thickness of epidermis decreased in dorsal skin tissue. Conclusions SEI can regulate allergic inflammatory response suppressed the gene expression and production of cytokines that mediate allergic reactions, and will be able to be effectively utilized in the treatment of atopic dermatitis future.

• The Journal of Pediatrics of Korean Medicine
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• v.21 no.1
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• pp.87-116
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• 2007

Objectives : The purpose of this study is to examine of the effect of Kami-chungsimyeunjatang(KCSYJT) medicine on the atopy eruption control. Methods : The expression of IgE, IL-4, IL-6, $TNF-{\alpha}$, IgG2b, IgM, IgG2a and IgG1 level in serum, and $IFN-{\gamma}$ production by KCSYJT were analyzed. CD3e+/CD69+, CD4+/CD25+, B220+/IgE+ and B220+/CD23+ positive cells by flow cytometry in splenocytes were assayed and the revelation of CD3e+/CD69+, CD4+/CD8+ and CD4+/CD25+ marker in PBMC, spleen and DLN were observed. The outturn of IL-4, eotaxin 2, CCR3, TARC mRNA in splenocytes werw observed. We also analyzed NC/Nga mice's ear, DLN and neck-back skin after biopy and dye by H&E, and toluidine staining (mast cells marker) method, measured about epidermis and dermis part in comparison with control group. Results : NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction. Specially, result that measure IgE content in serum on 8 weeks, 12 weeks, 16 weeks decreased remarkably than control group. After experiment end, result that observe revelation CD3e+/CD69+, CD4+/CD8+ and CD4+/CD25+ marker in PBMC, spleen and DLN establishment observed recover as normal with political background. And decreased than result control group which measure IL-4, IL-6, $TNF-{\alpha}$, IgG2b, IgM, IgG2a, IgG1 level in serum, and $IFN-{\gamma}$ production secreted in Th1 cell displayed increase by KCSYJT medicines. Ear thickness decrease than control group in result that observe effect that get in ear of a NC/Nga mouse. Course inflammation immunocyte etc.. permeated of result that effect that KCSYJT medicines get to NC/Nga mouse's skin establishment analyzes ear, DLN and neck-back skin after biopy, and dye by H&E, and toluidine staining (mast cells marker) method decreased about epidermis. and inflammation of dermis part remarkably than control group. Immunohistochemical examination of the skin lesion showed decrease by KCSYJT medicines on numbers of mast cells (CCR3) and CD4+ T cells containing IL-4 necessary for IgE. Conclusions : Th1 cell and Th2 cell was observed to be shift by secretion amount of IL-4 and $IFN-{\gamma}$ by KCSYJT medicines. Therefore, the KCSYJT medicine turned out to be useful in allergy autoimmune disease.

• Molecules and Cells
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• v.20 no.3
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• pp.339-347
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• 2005

IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory cytokines, and emerging evidence indicates that it plays a central role in inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T cells, but relatively little is known about how its expression is regulated. In the present study, we examined the requirements and mechanisms for IL-17 expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced rapidly in primary T cells after stimulation of the T cell receptor (TCR) through CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is different in mice than in humans, because "costimulation" of T cells through CD28 only mildly enhanced IL-17 expression, whereas levels of IL-2 were dramatically enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB and CD40L exerted only very weak enhancing effects on IL-17 production. In agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression. However, IL-17 production can occur autonomously in T cells, as neither dendritic cells nor IL-23 were necessary for promoting short-term production of IL-17. Finally, to begin to characterize the TCR-mediated signaling pathway(s) required for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and MAPK signaling pathways.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.2
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• pp.65-81
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• 2016

Objectives : Haedoksamul-tang (HSTE), a water extract from a mixture of Phellodendri Cortex, Coptidis, Scutellariae Radix, Gardeniae Fructus, Angelica acutiloba Radix, Cnidii Rhizoma, Paeoniae Radix, Rehmanniae Radix, has been traditionally used for allergic skin diseases such as atopic dermatitis and contact dermatitis in oriental countries. However, little is known about the effects of aqueous extract of HSTE on trimellitic anhydride (TMA)-induced contact hypersensitivity (CHS) in a mouse model. Methods : In this study, we investigate the pharmacological effects of HSTE on TMA-induced CHS in Balb/c mice. Contact hypersensitivity was induced in mice by topically sensitizing and challenging with TMA in flank skin and ears during oral administration (for 17 days) and topical treatment (30 min before challenge) with HSTE. We examined the effects of HSTE on IgE and IgG1 levels, inflammatory parameters in ear tissues, CD4⁺/CD8⁺ ratio, cytokine and chemokine production in sera, tissues, and immune cells from TMA-sensitized mice.Results : Oral and topical administration with HSTE reduced, in a dose dependent manner, thickness and leukocyte infiltration of ear tissues and IgE levels in serum from mice sensitized with TMA. In addition, auricula lymph node cells isolated from TMA-sensitized mice significantly elevated the expression ratio of CD4⁺/CD8⁺ as well as increased the production of IL-4, IL-5, IL-13 and IFN-γ by ex vivo stimulation with antibodies against CD3 and CD28, and these inflammatory indexes, except for IFN-γ, were significantly suppressed by orally and topically administration of HSTE. Furthermore, stimulation of auricula lymph node cells from TMA-sensitized mice with antibodies against CD3 and CD28 increased the production of MCP-1/CCL2 and MIP-1α/CCL3, and these effects were inhibited in a dose-dependent manner in cells from mice treated with HSTE. Conclusions : These results suggest that HSTE can be used for treating contact hypersensitivity by inhibiting leukocyte infiltration as well as production of serum IgE and chemokine/Th2 cytokine in an animal model.

• The Journal of Pediatrics of Korean Medicine
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• v.25 no.1
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• pp.1-27
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• 2011

Objectives: The purpose of this study is to investigate the effects of Yijungtang(YJT) on atopic dermatitis in an in-vitro and in-vivo experiment using a RBL-2H3 mast cells and a NC/Nga atopic dermatitis mouse. Methods: In-vitro experiment, IL-4, IL-13 mRNA expression were evaluated by a real-time PCR, IL-4, IL-13 production by ELISA and transcription factor as GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-kB by western blotting. In-vivo experiment, clinical skin score we evaluated by, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mouse, cytokine level, total number of cell, Immunohistochemical staining and Histological features of auxiliary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue in NC/Nga mouse. Results: YJT decreased IL-4, IL-13 mRNA expression, IL-4, IL-13 production and prominently decreased the expression of mast cell specific transcription factors including GATA-2, NF-AT2, c-Fos and NF-kB. YJT oral administration reduced the levels of skin severity scores. It also decreased the level of inflammatory cytokines such as IL-5, IL-13, histamine and IgE in the serum. It elevated IFN-gamma level in the spleenocyte culture supernatant but decreased. $CD3e^+$, $CD19^+$, $CD4^+$, $CD8^+$, $CD3e^+CD69^+$, $CD11b^+Gr-1^+$, $CCR3^+$ in the PBMCs, $CD4^+$, $CD8^+$, $CD3e^+CD69^+$, $B220^+CD23^+$ in the ALN, $CD4^+$, $CD3e^+CD69^+$ in the ALN and $CD4^+$, $CD11b^+Gr-1^+$ in the dorsal skin. Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mice were much improved by YJT oral administration. Conclusions: The anti-allergic activities of YJT may be mediated by down-regulation of Th2 cytokines, such as IL-4 and IL-13, through the regulation GATA-2, NF-AT2 and NF-kB transcription factors in mast cells. YJT would be regulate molecular mediators and immune cells which are functionally associated with atopic dermatitis induced in NC/Nga mice, and may play an important role in recovering AD symptoms.

• The Journal of Internal Korean Medicine
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• v.29 no.2
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• pp.456-468
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• 2008

Objective : The purpose of this study was to investigate the effects of Gamisagunja-tang(GS) on the airway hyper-reactivity (AHR), cytokine production and T cell activation during the ovalbumin (OVA)-induced allergic asthma in mice. Materials and Methods : BALB/c mice were sensitized and challenged with 100 mg of OVA and 1 mg of aluminum potassium sulfate intraperitoneally on days 1 and 7. On day 14, mice were challenged on 3 consecutive days with 5% OVA. AHR and bronchoalveolar fluid (BALF), total inflammatory cell count and the production of cytokines were measured. Results : GS significantly suppressed the infiltration of inflammatory cells in the lung tissue and AHR. GS significantly down regulated the production of IL-4, IL-5 and increases of $INF-{\gamma}$ in BALF. GS reduced the population of eosinophils from lung and spleen in OVA-induced allergic asthma. GS reduced the population of $CD4^{+}$ $CD69^{+}$ $CD25^{-}$ T cells in OVA-induced allergic asthma Conclusion : These results suggest that GS may inhibit the production of IL-4, IL-5 and infiltration of eosinophils and be beneficial oriental medicine for allergic asthma.

• Natural Product Sciences
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• v.17 no.4
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• pp.354-362
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• 2011

Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by abnormalities in T cell immunoregulation and hyperreactivity of B cells, leading to autoantibody production and multiorgan injuries. We investigated the effect of baicalin on aberrant immunoregulation in pristane-induced lupus mice. Mice received i.p. a single injection of 0.5 ml of pristane or PBS, and approximately 3 months later, were used as a pristane-induced lupus model or healthy controls. The pristane-induced lupus mice and healthy mice were randomly divided into three groups: healthy mouse group (healthy control), pristane-primed lupus control group (lupus control), and baicalin (BAC)-treated pristane-primed lupus mouse group (BAC-treated lupus). The pristane-induced lupus mice and healthy mice were administrated orally with BAC 50 mg/kg or PBS once in a day for 10 ds. These results demonstrated that levels of serum IL-6, LPS-induced production of IL-6, $PGE_2$ and NO by macrophages, $PGE_2$-stimulated production of IL-6 by macrophages and IFN-${\gamma}$ by thymocytes, and an overexpression of splenic NKT cells and CD69+CD4+ T cells were downregulated in BAC-treated lupus compared to lupus control, while reduced apoptosis of splenic CD4+ T cells were upregulated. Therefore, these findings suggest that BAC may attenuate autoimmunity and disease activity in lupus via downregulation of aberrant activation of T cells and inhibition of overproduction of IL-6 and $PGE_2$ in pristane-induced lupus mice.

• Korean Journal of Pharmacognosy
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• v.29 no.2
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• pp.110-119
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• 1998

Sa-Mul-Tang(SMT) consist of Rehmanniae Radix Preparata, Paeoniae Radix Alba, Cnidii Rhizoma and Angelicae Gigantis Radix. In L1210 cells-transplanted BALB/c mice, T-lymphocyte apoptosis, $CD8^+T_C$ cells population in thymocyte and nitric oxide production in macrophage were enhanced, but phagocytic activity was decreased. SMT suppressed T-lymphocyte apoptosis and enhanced CD^4+T_H$ cells population, but did not affect nitric oxide production and phagocytic activity in L1210 cells-transplanted mice. In antitumor drugs-injected mice, T-lymphocyte apoptosis was enhanced, but $CD4^+T_H/CD8^+T_C$, cells population and T-lymphocyte proliferation were decreased. SMT suppressed T-lymphocyte apoptosis, and enhanced $CD8^+T_C$ cells population, T-lymphocyte proliferation and phagocytic activity in vincristine-injected mice. These results suggest that SMT enhances T cell-mediated immunity in L1210 cell-transplanted mice, and enhances T cell-mediated immunity and phagocytic activity in vincristine-injected mice.