• IMMUNE NETWORK
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• v.5 no.3
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• pp.137-143
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• 2005

Background: Millions of people in the world are suffering from atopic dermatitis (AD), which is a chronic inflammatory skin disease triggered by Th2 immune responses. The NC/Nga mouse is the most extensively studied animal model of AD. Like human AD, NC/Nga mice demonstrate increased levels of IgE, a hallmark of Th2 immune responses. Adaptive immunity cannot be generated without help of innate immunity. Especially natural killer T (NKT) cells and marginal zone B (MZB) cells have been known to play important roles in linking innate immunity to adaptive immunity. Methods: Through flow cytometric analysis and ELISA assay, we investigated whether these lymphocytes might be altered in number in NC/Nga mice. Results: Our data demonstrated that the number of NKT cells was reduced in NC/Nga mice and IFN${\gamma}$ production by NKT cells upon ${\alpha}-GalCer$ stimulation decreased to the levels of CD1d KO mice lacking in NKT cells. However, reduction of NKT cells in NC/Nga mice was not due to CD1d expression, which was normal in the thymus. Interestingly, there was a significant increase of $CD1d^{high}B220^+$ cells in the spleen of NC/Nga mice. Further, we confirmed that $CD1d^{high}B220^+$ cells are B cells, not dendritic cells. These $CD1d^{high}B220^+$ B cells show $IgM^{high}CD21^{high}CD23^{low}$, a characteristic phenotype of MZB cells. Conclusion: We provide the evidence that there are decreased activities of NKT cells and increased number of MZB cells in the NC/Nga mice. Our findings may thus explain why NC/Nga mice are susceptible to AD.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.1
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• pp.116-134
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• 2005

Although the parallel prescription of Sopoongsangagambang (SG) administration along with external treatment such as spraying or ointment application on the skin is clinically used for the treatment of atopic dermatitis (AD), molecular mechanism underlying its effectiveness is unknown. Thus in the present study, diverse immune responses in terms of chemical mediators related to AD were investigated using an atopic mouse model NC/Nga after SG administration and external treatment (ET), and major findings are summarized as follows. 1. The clinical severities in 16 and 20 week old NC/Nga mice with SG and ET treatment were decreased to 72.2% and 62.3% respectively compared to the control NC/Nga mice with no drug treatment. 2. IgE, IL-4, IL-5, IL-6, IL-13, IgM, IgG1 and IgG2a levels in the serum of SG and ET treated NC/Nga mouse group were significantly decreased compared to the untreated control mice. In contrast, $IFN-{\gamma}$ showed a significant increase in the experimental group compared to the untreated control group. 3. The spleen weight of SG and ET treated NC/Nga mice was significantly decreased compared to the untreated control group. 4. The B/T ratio in the lymph node of SG and ET treated NC/Nga mice was increased compared to the untreated control group. $CD4^+\;and\;CD8^+$ cell numbers in the lymph node of SG and ET treated NC/Nga mice were significantly increased compared to the untreated control group, but $CD69^+\;and\;CD11a^+$ cells were significantly decreased. 5. mRNA expression levels of IL-4, IL-5, and CCR3 in the skin tissues of SG and ET treated NC/Nga mice were significantly decreased, and expression levels of IL-6, IL-13, $CD69^+/CD3{\varepsilon}^+\;and\;CD19^+/CD44^+$ in the skin tissues of SG and ET treated NC/Mga mice were significantly decreased compared to the untreated control group. $IFN-{\gamma}$ mRNA expression levels were increased compared to the untreated control group. 6. Histological observation of the ear and neck skin tissues showed that the extents of inflammation and infiltrated immune cells in the epidermis and dermis of SG and ET treated NC/Nga mice were highly reduced compared to the untreated control group. 7. Lymphokine assay showed a significant decrease in IL-4 levels in SG and ET treated NC/Nga mice compared to the untreated control group, but the levels of $IFN-{\gamma}$ secretion were significantly increased drug treated NC/Nga mice.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.1
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• pp.27-49
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• 2005

당귀음자가감방(當歸飮子加減方)과 외치방(外治方) 병용의 아토피 치료 기전을 규명하고자 NC/Nga 생쥐의 동물 병태 모델을 이용하여 다양한 면역 반응을 관찰하였던 바, 다음과 같은 결론을 얻었다. 1. NC/Nga 생쥐의 피부손상 정도 16주와 20부에 대조군에 비해 36.0%, 37.8% 감소하다. 2. NC/Nga 생쥐의 혈중(血中) IgE, IL-4, IL-5, IL-6, IgM, IgG1 및 IgG2a 수준은 대조군에 비하여 유의성 있게 감소하였고, IL-13 수준은 대조군에 비하여 감소하였으나 유의성을 나타내지 않았다. 반면, $IFN-{\gamma}$ 수준은 유의성 있게 증가하다. 3. NC/Nga 생쥐의 비장 무게는 대조군에 비하여 유의성있게 감소하였다. 4. NC/Nga 생쥐의 lymph node에서 B/f ratio는 증가된 대조군에 비하여 감소하였으며, $CD4^+$와 $CD8^+$ 세포 발현은 대조군에 비하여 증가하였고, $CD4^+$는 유의성있는 감소를, $CD8^+$는 유의성 없는 약간의 증가를 나타내었다. $CD69^+$, CD11a 세포 발현은 대조군에 비하여 유의성있게 감소하였다. 5. NC/Nga 생쥐의 피부조직배양에서 IL-4 IL-5, CCR3 유전자 발현은 대조군에 비하여 현저히 감소하였고, IL-6, IL-13, $CD69^+/CD3{\varepsilon}^+,{\;}CD19^+/CD44^+$ 발현량은 유의성있게 감소하였으며, $IFN-{\gamma}$의 유전자 발현은 대조군에 비하여 증가하였다. 6. NC/Nga 생쥐 귀, 목의 피부 조직 변화에서는 표피와 진피의 염증 정도와 침윤된 염증 면역세포 등이 대조군에 비하여 현저하게 감소되었다. 7. Lymphokine assay에서 IL-4 발현량은 대조군에 비하여 유의성 있게 감소(減少)하였고, $IFN-{\gamma}$의 발현량은 유의성 있게 증가하였다.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.95-101
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• 2015

Objectives : The aim of this study was to confirm whether or not coral has a preventive effect on development of atopic dermatitis induced by house mite(dermatophagoides pteronyssinus) in NC/Nga mice. Methods : This study was undertaken by using a reliable Atopic dermatitis mouse model demonstrating similar immune response. Lobophytum crassum was administered orally to NC/Nga mouse for 3 weeks. In order to verify the effectiveness of Lobophytum crassum in atopic dermatitis treatment, its role in immune factors were observed in NC/Nga mice. Results : ALT, AST, BUN and creatine levels were all within in the normal ranges in MC-1 200 and 400 (mg/kg) treated groups, indicating no induced toxicity. MC-1 200 and 400 (mg/kg) groups decreased of atopic dermatitis skin manifestation in NC/Nga mouse of MC-1 200 and 400 (mg/kg) groups compared to that of the control group and decreased the ratio of WBC and lymphocyte in blood. Also, MC-1 200 and 400 (mg/kg) groups significant decreased the ratio of CD4+, CD8+, CD11b+/Gr1+, B220/CD23 and CD4/CD25 immune cell ratio in ALN. Finally MC-1 200 and 400 (mg/kg) groups significantly increased the ratio of CD4+, CD8+, B220/CD23 and CD4/CD25 immune cells in DLN. Conclusions : Theses results suggested that Lobophytum crassum has suppressive effects on aberrant and overactive immunological activities in dermatophagoides pteronyssinus-induced dermatitis mice of NC/Nga.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.679-687
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• 2007

The purpose of this study is to examine closely effect that Onchung-eum(OC) and Samhwangseze-gamibang(SG) used to atopic dermatitis disease patient get in atopy eruption control experimentally. Atopic dermatitis(AD) of molecular mechanism underlying it's effectiveness is unknown. We analyzed the expression the clinical severities in 13 and 16 weeks old NC/Nga mice, and the spleen weight of OC with SG treated NC/Nga mice, and mRNA expression levels of IL-4, IL-5, and CCR3 in the skin tissues of OC with SG treated NC/Nga mice, and IL-1${\beta}$, TNF-${\alpha}$, IL-6 express of gene, and Histological observation of the ear and skin tissues, and than IgE, IL-4, IL-5, IL-6, IgM, IgGl levels in the serum of OC with SG treated NC/Nga mouse group compared to the untreated control mouse group. Also, We examined cell toxicity that of OC is safety the strength of 10, 50, 100ppm and inflammatory RAW 264.7 in the serum of OC. Thus in these present study diverse immune responses in terms of chemical mediators related to AD were investigated using an atopic mouse model NC/Nga after OC along with 5G. At the result that OC along with SG treat is can effective use for the treatment of atopic dermatitis(AD).

• Journal of Haehwa Medicine
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• v.17 no.2
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• pp.185-198
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• 2008

Wished to examine closely effect that Atopy cream-Jawoongo ointment (A-J) used to atopy dermatitis disease patient get in atopy eruption control experimentally. In this research A-J ointment as treatment result to a NC/Nga mouse by BMAC ointment, clinical skin severity score decreased remarkably than control group. Thus, NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction. Specially, result that measure IgE and IgG1 level in serum decreased remarkably than control group.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1210-1218
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• 2007

Recently Atopic Dermatitis(AD) is increasing along with allergic disease. At present, there is no infallible cure for AD. Then AD patients undergo great suffering. This study is carried out to see whether or not the administering Danggwieumja(DG) along with Samhwangseje-gamibang(SG} as a medicine for external aplication, is effective in treating atopic dermatitis. To examine the effectiveness of the above prescription, the author made an observation of diverse immune responses. through the model of NC/Nga atopic mice. Results provided evidence that the DG administration along with SG can be used as a treatment means to atopic dermatitis. The results are as follows: The extent of Clinical skin severities in 13 and 16 week old NC/Nga mice treated with DG and SG, were reduced by 50.9%, 53.9% respectively, compared to the control NC/Nga mice with no drug treatment. IgE, IL-4, IL-5, IL-6, IgM and IgG1 levels in the serum of the NC/Nga mice treated with DG and SG were significantly decreased compared to those of the untreated control mice. In contrary, to the $IFN-{\gamma}$ level, significantly increased. The spleen weight of the NC/Nga mice treated with DG and SG significantly decreased compared to those of the untreated control mice. CCR3 gene expression in the skin tissue of NC/Nga mice treated with DG and SG were highly decreased, and the IL-6 expression significantly decreased, and the $IFN-{\gamma}$ gene expression increased compared to those of the untreated control mice. Histological observation of the ear and dorsal skin tissue of the NC/Nga mice treated with DG and SG, showed that the extents of inflammation and infiltrated immune cells in the epidermal tissue and dermis, were highly reduced compared to those of the untreated control mice. In the model inducing COX-2 activity in RAW 264.7 cell, the denser DG became, the more COX-2 activity was inhibited, compared to those of the untreated control group. $IL-1{\beta}$, and $TNF-{\alpha}$, IL-6 gene expression in RAW 264.7 cell with DG, significantly decreased, compared to those of the untreated control group. According to the assessment of cell toxicity in L929 cell, the rate of cell multiplication increased by 3% in consistency to 100ppm of DG compared to the untreated control group and in more than the 200 ppm consistency, cell toxicity was occurred.

• Science of Emotion and Sensibility
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• v.19 no.2
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• pp.27-34
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• 2016

The effects of aroma mixed oil with Chamomile, Lavender and Sandalwood on atopic dermatitis in NC/Nga mice were examined. The NC/Nga mice were divided into BMAC group, FK 506 Oinment (Tacrolimus Hydrate) group, and CLS group to get curative power of CLS. The amount of total IgE and IgG1 was measured and the severity of atopic dermatitis was assessed by the scoring procedure in NC/Nga mice. Topically applied CLS significantly suppressed the level of serum IgE and IgG1 in NC/Nga mice and FK506, used as reference drugs for atopic dermatitis, also exhibited suppressive effects against level of IgE and IgG1. The level of IgE was lower in the CLS group than in the FK506 group while the serum IgG1 level in the FK506 group was lower than in the CLS group. The treatment with FK506 and CLS reduced the skin inflammation index, especially the severity degree of atopic dermatitis in the skin lesioned NC/Nga mice by naked eyes was improved by treatment of FK506 and CLS. The results suggest that treatment of CLS in NC/Nga mice with atopic dermatitis have an beneficial therapeutic effects on reducing the level of IgE and IgG1 and accelerating repair of skin lesion.

• BMB Reports
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• v.40 no.4
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• pp.486-493
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• 2007

Atopic dermatitis (AD) is a chronic inflammatory skin disease and the pathogenesis of AD is associated with the release of various cytokines/chemokines due to activated $Th_2$ immune responses. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotide in the context of particular base sequence (CpG motifs) are known to have the immunostimulatory activities in mice and to convert from Th2 to Th1 immune responses in AD. We aimed to investigate that CpG ODN, especially phosphodiester form, can stimulate the protective immunity in NC/Nga mice with AD. We isolated BMDCs from NC/Nga mice and then, cultured with GM-CSF and IL-4 for 6 days, and treated for 2 days by either phosphorothioate ODN or phosphodiester ODN. CpG ODN-treated DCs resulted in more production of IL-12. When CpG ODN-treated DCs were intravenously injected into the NC/Nga mice, the NC/Nga mice with CpG ODN-treated DCs showed significant improvement of AD symptoms and decrease of IgE level. Histopathologically, the NC/Nga mice skin with CpG ODN-treated DCs showed the decreased IL-4 and TARC expression comparing with non-injected mice. These results may suggest that phosphodiester CpG ODN-treated DCs might function as a potent adjuvant for AD in a mouse model.

• The Journal of Pediatrics of Korean Medicine
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• v.22 no.3
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• pp.105-137
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• 2008

Objectives : The purpose of this study is to investigate the effect of Gupoongjeseuptang (GPJST) on atopic dermatitis by in vivo experiment using NC/Nga atopic dermatitis mouse, which has histological and clinical similarities to the atopic dermatitis of human. Methods : To investigate the effect of GPJST on atopic dermatifis, we evaluated atopic dermatitis-like skin lesions by clinical skin index and analyzed immunological parameters in peripheral blood mononuclear cells (PBMCs), splenocytes, draining lymph node (DLN) and performed skin histology in ears and dorsal skin of atopic dermatitis-like skin NC/Nga mouse in vivo. Results : In vivo, clinical skin severity score were significantly lower in GPJST group than control group. IgE, IL-6, $TNF-{\alpha}$, IgG1, IgM, IgG2a and IgG2b levels in serum decreased remarkably in GPJST group than control group. Also, total absolute number of $CD3^+CD69^+$, and $CCR3^+$ cells recovered as normal in PBMCs and $CD3^+$, $CD3^+CD69^+$ decreased significantly compared with control group in isolated DLN from NC/Nga mouse and total absolute number of $CD11b^+Gr-1^+$, $CCR3^+CD3^+$ in dorsal skin of NC/Nga mouse decreased by GPJST. We analyzed ear and neck-back skin after biopsy and dyeing by hematoxyline/eosin (H&E) and toluidine staining (mast cells marker) and obtained results that GPJST are very effective to histological symptoms (dermal and epidermal thickening, hyperkeratosis and inflammatory cell (CD4, $CCR3^+$) infiltration). Conclusions : This study demonstrates immunological activity of GPJST on atopic dermatitis-like model mice.