• Biomolecules & Therapeutics
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• 제28권6호
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• pp.537-541
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• 2020

Sphingosine-1-phosphate (S1P) and its receptors have been implicated in atopic dermatitis. S1P₂ was found to function as a proallergic receptor, while its antagonist JTE-013 was found to suppress allergic asthma in mice. Topical application of JTE-013 has not been investigated in an in vivo model of atopic dermatitis. Therefore, the therapeutic potential of JTE-013 topical application was evaluated by the use of a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. DNCB-induced inflammation and mast cell accumulation in skin tissues were significantly suppressed by topical JTE-013 treatment in BALB/c mice. DNCB-induced increase of lymph nodes sizes and elevated inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in lymph nodes were also significantly reduced by the JTE-013 treatment. Elevated serum levels of IgE were significantly suppressed by the topical treatment of JTE-013. In summary, the topical treatment of JTE-013 S1P₂ antagonist suppressed DNCB-induced atopic dermatitis symptoms and immune responses. These results suggested JTE-013 as a potential therapeutic agent for atopic dermatitis.

• 대한한방소아과학회지
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• 제28권3호
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• pp.59-73
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• 2014

Allergic contact dermatitis (ACD) is a type IV delayed hypersensitivity reaction that results from exposures and subsequent sensitization to an environmental chemical. Crataegus Pinnatifida (CP) is commonly used to improve spleen function, remove retention of food, and promote blood circulation. This study is designed to investigate the effects of CP on ACD induced by 2,4-dinitrochlorobenzene (DNCB) in mice. In this experiment, the effects of CP on changes in body weights, ear and dorsum skin thicknesses, ear weights, clinical aspects on the dorsum skin, histopathological changes, spleen weights, cytokines were investigated. In addition, the effects on the proliferation rates of splenocytes were also investigated in vivo and vitro study. In results, CP spread (CPS) group and CP spread and administered (CPS+Adm) group showed decrease in spleen weights. In CPS+Adm group, dorsum skin thicknesses were decreased significantly compared to control group. CP treatment diminished erythema, desquamation and keratosis which were induced by repeated painting of DNCB. In histopathological observation, spongiosis and edema were diminished in CPS and CPS+Adm group. CP led to decrease in the proliferation rates of splenocytes in vivo and vitro. In conclusion, these data suggest that CP can decrease symptoms of ACD, so CP is useful to treat patient with ACD.

• 대한한방소아과학회지
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• 제29권2호
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• pp.1-15
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• 2015

Objectives In the theory of Korean Medicine, Cicadae Periostracum (CP) has been used to treat skin diseases such as inflammatory dermatitis, tetanus and pruritus. CP can reduce heat and disperse wind. In prior studies, anti-allergic effect and anti-inflammatory effect of CP were reported. However, there has been no report regarding the correlation of CP and allergic contact dermatitis (ACD). This study was performed to show the effects of CP in ACD induced by 2,4-dinitrochlorobenzene (DNCB) in mice. Methods In this experiment, the effects of CP on biological changes were measured, such as changes in ear and spleen weight, ear and dorsum skin thickness, clinical aspect on the dorsum skin and histological changes. The effect of proliferation rate of splenocytes was also investigated in vitro and vivo study. Results In results, CP application (CPA) group and CP application and administration (CPAA) group were significantly restrained in ear weight gain and increase in ear and dorsum skin thickness compared to the control group. In addition, CPA and CPAA group showed diminished erythema, desquamation, bloodstain, and marks. Also, the histological assessment showed that CP treatement diminished thickness of epidermis, hyperkeratosis, pigmentation and parakeratosis. Conclusions In conclusion, these data suggest that CP can decrease symptoms of ACD.

• Toxicological Research
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• 제22권4호
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• pp.357-364
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• 2006

This study was undertaken to develop a reliable mice model demonstrating similar immunologic phenomena as human atopic dermatitis characterized with predominance of type-2 immune response. BALB/C mice and NC/Nga mice were sensitized twice with $100{\mu}l$ of 1% 2,4-dinitrochlorobenzene (DNCB) or vehicle (acetone : olive oil=4:1 mixture) in a week and challenged twice with $100{\mu}l$ of 0.2% DNCB or the vehicle at the following week. Mice were sacrificed at 19 days following the second DNCB or vehicle challenge for NC/Nga mice and at 28 days following the second DNCB or vehicle challenge for BALB/c mice. Upregulation of plasma 1gE, a hallmark of atopic dermatitis occurrence, was evident in the plasma obtained 4 day after the second DNCB challenge from BALB/c mice (approximately 4-fold) and NC/Nga mice (approximately 6-fold) treated with DNCB in comparison with that of the vehicle treated-control mice, and remain higher $3{\sim}4$ week after the second challenge. Ratio of plasma IgG1 versus IgG2a concentration was significantly higher in the mice treated with DNCB than the control mice, which also implies the skewed type-2 reactivity in vivo. Ratio of interleukin-4 versus interferon gamma produced in the splenic T cell culture supernatants was approximately 3-fold higher in the both strains of mice treated with DNCB than their control mice, respectively. The DNCB-treated mice demonstrated atopic dermatitis-like skin legions characterized with erythma, scaling, and hemorrhage, which was not observed with the control mice. Scratching on face or dorsal area was significantly more frequent (approximately 25-fold) in the DNCB-treated mice than the control at next day of the second DNCB challenge, and scratching frequency remains higher (approximately 4-fold) in the mice treated with DNCB than the control at 14 day following the second DNCB challenge. Overall, the mice model developed through sensitization and challenge with DNCB may be useful for research on atopic dermatitis and development of treatment materials for atopic dermatitis.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2005년도 춘계 국제심포지엄 및 학술대회
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• pp.141-141
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• 2005

• 대한수의학회지
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• 제24권2호
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• pp.169-171
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• 1984

An expeliment was carried out to measure the cellular immune response in guinea pigs by sensitizing the animals with 2, 4-dinitrochlorobenzene(DNCB). The guinea pigs could be sensitized with one application of DNCB. The sensitizing and challenge dose was standardized. The histological response was characteristic of a delayed hypersensitivity reaction.

• 한방안이비인후피부과학회지
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• 제27권3호
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• pp.115-132
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• 2014

Objective : Portulacae Herba (PH) can clear away heat, detoxicate, cool down blood heat. The present study was designed to investigate the effects of PH on ACD induced by 2,4-dinitrochlorobenzene (DNCB) in mice. Method : In this experiment, the effects of PH on changes in body weights, thicknesses and weights of ear, thicknesses of dorsum skin, degree of symptoms on the dorsum skin, histopathological changes of ear and dorsum skin, spleen weights, TNF-${\alpha}$ and IL-10 in serum were observed. And the effects on the proliferation rates of splenocytes were also investigated in vitro and in vivo. Results : 1. PH spread (PHS) group and PH spread plus administered (PHS+Adm) group didn't show any changes in weight and thickness of ear. 2. But in PHS and PHS+Adm group, thickness of dorsum skin decreased significantly. 3. And PHS and PHS+Adm group showed meaningful effectiveness on ACD symptoms like erythema, desquamation and keratinization. 4. In histopathological observation, hyperplasia and edema of spongy tissues were remarkably diminished in PHS and PHS+Adm group. 5. And PH reduced the proliferation rates of splenocytes in vivo and vitro study. Conclusions : PH effectively decreased symptoms of ACD in this study, therefore PH can be one of medicinal ingredients to treat ACD.

• Toxicological Research
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• 제34권1호
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• pp.7-12
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• 2018

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T ($T_H1$) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of $T_H1$ cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

• Toxicological Research
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• 제19권2호
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• pp.133-139
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• 2003

Allergic contact dermatitis may be caused by a wide variety of chemicals. A murine local lymph node assay (LLNA) has been developed as an alternative to guinea pig models for assessing the contact sensitization potential of chemical. However, there is a need to develop a nonradioisotopic endpoint for the LLNA, because of the radioisotopic method's requiring the use of special facilities. In this study, we investigated the development of a nonradioisotopic endpoint for LLNA using ELISA (enzyme-linked immunosorbent assay). Female Balb/c mice were treated by the topical application on the dorsum of both ears with four different strong sensitizers, 2,4-dinitrochlorobenzene (DNCB), oxazolone (OXZ), toluene diisocyanate (TDI), and trimellitic anhydride (TMA), and a strong irritant, sodium lauryl sulfate (SLS), once daily for three consecutive days. The proliferation of cells in the auricular Iymph node was analyzed by means of the labelling index (Ll) of bromodeoxyuridine (BrdU) incorporation into cells. The weights of the Iymph nodes in the mice treated with allergens, DNCB, OXZ, TDl and TMA were increased compared to the vehicle control. The stimulation index (Sl) of mice treated with DNCB, OXZ, TDl, and TMA was over three-fold increase compared to the vehicle control. However, the S1 of mice exposed to SLS was not significantly increased compared to the vehicle control, while the lymph node weight of SLS was significantly increased. These results suggest that the LLNA modified endpoint using ELISA based on BrdU incorporation could provide a useful method of screening for irritants and allergens.

• 생약학회지
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• 제40권3호
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• pp.218-223
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• 2009

The roots of Rumecis Radix have been used for the treatment of heat phlegm, jaundice, constipation, scabies and uterine hemorrhage. The aim of this study was to confirm whether Rumecis Radix water extract (RJWE) has a preventive effect on the development of atopic dermatitis (AD) in 2,4-dinitrochlorobenzene (DNCB)-applied BALB/c mice. Oral administration (12.5 mg/kg, 25 mg/kg) and topical application (0.5 mg/mouse, 1.0 mg/mouse) of RJWE decreased the development of AD-like skin lesions, ear swelling, spleen weight and total serum IgE. RJWE significantly also inhibited the infiltration of mast cells in the dorsal skin. Furthermore, the release of histamine from rat peritoneal mast cells (RPMCs) was suppressed significantly. These results suggest that the inhibitory effect of RJWE on AD might be associated with mast cells.