• 대한한의학회지
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• 제19권1호
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• pp.419-429
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• 1998

Poncirus trifoliata (L.) Raf (Rutaceae) fruits (PTFE) has been used for the treatment of allergic disease. IgE is normally one of the least abundant immunoglobulin (Ig) isotypes in the serum of both humans and several species of experimental animals: however a number of different stimuli can result in profound increases in IgE levels relative to other isotypes. In rodents, infection with many parasitic helminths can cause approximately 100-fold elevation in IgE within 2 wks. Immunization of mice with small amounts of protein antigens on alum also results in 10-fold to fold increase in total serum IgE, much of it specific for the immunizing antigen. In this experiment, I investigated the effect of an aqueous extract of Poncirus trifoliata (L.) Raf (Rutaceae) fruits (PTFE) on a in vivo and in vitro IgE production. PTFE dose-dependently inhibited the serum levels of IgE induced by antigens. The regulation of IgE synthesis is influenced by T cells and T cell derived factors. IL -4, a T cell-derived cytokine, has been shown to stimulate murine IgE synthesis both in vitro and in vivo. Current evidence suggests that IL-4 induces IgE synthesis in the mouse by stimulating H chain isotype switch. Lipopolysaccharide (LPS) plus IL-4 cause about l00-fold increase in IgE secretion by murine B cells. The effects of PTFE on the IL-4-dependent IgE response by mouse whole spleen cells were studied. Whole spleen cells were cultured for 7 days in the presence of LPS plus IL-4 and PTFE and the supernatants were assayed for IgE. IL-4 dependent IgE production of LPS-stimulated whole spleen cells was inhibited by PTFE. Moreover, in the present study using U266Bl human IgE-bearing B cells, I found that PTFE inhibited the production of IgE activated by LPS plus IL-4. These results indicate that PTFE have antiallergic activity by inhibition of IgE production from B cells.

• BMB Reports
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• 제33권6호
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• pp.454-462
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• 2000

Interleukin-4(IL-4) is known to be a major cytokine regulating immunoglobulin E(IgE) response by the induction of IgE production and type II IgE receptor(IgER II: CD23) expression. Recently, however, the role of neuroendocrine factors has been implicated in modulating the IgE response. Among various neuroendocrine growth factors, we investigated the effects of the insulin-like growth factor-1(IGF-1) since IL-4 and IGF-1 share common intracellular signaling molecules, such as the insulin receptor substrate-1/2(IRS-1/2) to induce a specific cellular response. In the human peripheral blood mononuclear cell (PBMC) cultures, IGF-1 was capable of inducing a substantial level of IgE production in a dose-dependent manner. It also noticeably upregulated the IL-4-induced or IL-4 plus anti-CD40-induced IgE production. Similarly, the IGF-1-induced IgE production was enhanced by IL-4 or anti-CD40 in an additive manner, which became saturated at high concentrations of IGF-1. Although IGF-1 alone did not induce IgER II (CD23) expression, it augmented the IL-4-induced surface CD23 expression in a manner similar to the action of anti-CD40. These results imply that IGF-1 is likely to utilize common signaling pathways with IL-4 and anti-CD40 to induce IgE and IgER II expression. In support of this notion, we observed that IGF-1 enhanced the IL-4-induced signal transducers and activators of transcription 6(STAT6) activation and independently induced $NF-{\kappa}B$ activation. Both of these bind to the IgE(C) or IgER II (CD23) promoters. Together, our data suggest that IL-4 and IGF-1 work cooperatively to activate STAT6 and $NF-{\kappa}B$. This leads to the subsequent binding of these transcription factors to the $C{\varepsilon}$ and CD23 promoters to enhance the expression of IgE and IgER II. The observed differential ability of IGF-1 on the induction of IgE vs. IgER II is discussed based on the different structure of the two promoters.

• 대한한의학회지
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• 제25권2호
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• pp.51-66
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• 2004

Objectives : To evaluate experimentally the clinical effect of Bojeongjeongcheon-tang, we observed the cytokines ($IL-1{\beta}$/TEX>, IL-4, IL-5, IL-6, IL-10, TNF-{\alpha},{\;}TGF-{\beta},{\;}IFN-{\gamma}$) and what effect they have on IgE in B cells of a rat. Methods : First of all, we extracted the spleens of healthy Balb/c mice and separated B cells from them. These B cells were cultured with anti-CD40 mAb (500 ng/ml), rmIL-4 (500 U/ml), Bojeongjeongcheon-tang (100 ug/ml, 10 ug/ml, 1 ug/ml). We used rmiL-10 (50 ng/ml) as a control group. Furthermore, we analyzed the expression of IgE, CD23, CD69 and the coherence of HRF in B cells using a flow cytometer. We also analyzed the cytokine gene expression in B cells by reverse transcriptase-PCR. We also measured B cells proliferation using the Liquid Scintillation Counter. Results : In this study, the Bojeongjeongcheon-tang treated group showed a tendency to decrease depending on the density compared with the control group in the expression of IgE+, CD23+, CD69, HRF. All of the Bojeongjeongcheon-tang treated group showed inhibitory effects with $IL-1{\beta}$, IL-4, IL-5 and proliferating effects with IL-6, IL-10, and $IFN-{\gamma}$ on cytokines transcript expression depending on the density. Meanwhile, $TNF-{\alpha}$ increased in all density. In IgE production, there was inhibitory effect on Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml) of significance (p < 0.01, p < 0.05). Also in B cell proliferation, the result revealed an inhibitory effect of Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml), of significance (p < 0.001, p < 0.01). Conclusions : This study shows that Bojeongjeongcheon-tang has an inhibitory effect on the production and activity of B cells. Also it inhibited CD23, IL-4 activity and IgE production and activation. It is obvious that Bojeongjeongcheon-tang treats asthma by inhibiting the production of histamine and HRF, IL-5 and proliferating IL-10. Also Bojeongjeongcheon-tang has some preventive effects on bronchial change by inhibiting $TGF-{\beta}$, which stimulates the bronchial transformation.

• 대한한방소아과학회지
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• 제21권1호
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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.

• 생명과학회지
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• 제17권11호
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• pp.1492-1496
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• 2007

CD40L를 발현하는 KU812세포와 CD40를 발현하는 항원 특이적 B 세포의 배양을 통해 IgE 클라스 스위치가 유도된다. 본 연구자는 체외면역법에 의해 건강인의 말초혈액을 이용하여 쌀 알레르겐 특이적 IgM 항체를 생성하는 B 세포주를 수립하였다. 본 연구에서는 KU812세포에 의한 쌀 알레르겐 특이적 IgE 항체의 유도를 시도하였다. 배양 전, 쌀 알레르겐 특이적 B 세포주, RA9G11과 PMA와 ionomycin을 6시간 처리하여 활성화된 KU812세포에서 CD40와 CD40L 발현량을 flow cytomerty를 통화여 각각 확인하였다. RA9G11세포와 활성화된 KU812세포는 높은 수준의 CD40와 CD40L를 각각 발현하였다. 쌀 알레르겐 특이적 IgE항체 합성 유도를 위해, 여러 가지 농도의 IL-4 존재하에, RA9G11세포와 활성화된 KU812세포를 12일 동안 배양하였다. IgE 정상영역의 mRNA 발현량과, 쌀 알레르겐 특이적 IgE 항체 생성 세포가 모든 조건에서 확인되었으며, 특히 50U의 L-4 농도 하에서 같은 비율의 RA9G11과 활성화된 KU812세포를 배양했을 때, IgE 합성이 가장 높았다. 따라서 활성화된 KU812세포에 의한 쌀 알레르겐 특이적 IgE 합성은 알레르기 질환의 치료 및 예방에 관한 연구에 기여할 것으로 사료된다.

• 한국식품과학회지
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• 제40권1호
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• pp.82-87
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• 2008

아토피 피부염에서 유산균의 유익성에 대해서는 이미 많이 알려져 있고 우리나라 전통식품인 김치유산균의 유익성에 대한 연구도 많이 진행되었으나 아토피 피부염에서 김치 유산균의 효과에 관한 연구는 아직 미비한 실정이다. 본 연구에서는 아토피 동물 모델인 NC/Nga mice에 김치유산균에서 추출한 유산균(L.plantarum K8)의 파쇄물과 유산균 및 ${\gamma}$-리놀렌산 복합체(L.rhamnosus GG 생균, B. lactis Bb-12Lb 생균, L. plantarum K8생균, L. plantarum K8 파쇄물, ${\gamma}$-리놀렌산)를 경구 투여한 후 혈청 면역지표(IgE, IL-4, IL-5, IFN-${\gamma}$)와 비장 배양액에서 IgE 농도를 측정하였다. 실험동물의 체중 및 사료섭취량은 사육기간이 지남에 따라 증가하는 경향을 보였으며 각 군 간에 유의적인 차이는 관찰되지 않았다. 실험 시작 시 혈청 IgE 농도는 각 군 간에 차이가 나타나지 않았으나 실험 전 기간 4주 동안 유산균 파쇄물(DPF), 유산균 및 ${\gamma}$-리놀렌산 복합체(DPOC), 항히스타민(DAH)을 섭취한 군에서 증류수(DDW)만을 섭취군에 비하여 유의적으로 낮게 나타났다. 혈청 IFN-${\gamma}$ 농도는 각 군에서 유의적인 차이가 나타나지 않았으나 혈청 IL-4 농도는 유산균 및 ${\gamma}$-리놀렌산 복합체를 섭취한 군(DPOC)에서 대조군에 비하여 유의적으로 낮게 나타났다. 혈청 IL-5 농도는 유산균 파쇄물(DPF), 유산균 및 ${\gamma}$-리놀렌산 복합체(DPOC), 항히스타민(DAH)을 섭취한 군에서 모두 대조군에 비하여 유의적으로 낮았다. 비장 임파구 배양 상층액의 IgE 농도는 각 군에서 군 간 유의적인 차이가 나타나지 않았다. 결론적으로, 아토피 동물모델 NC/Nga mice에 유산균 파쇄물(DPF)과 유산균 및 감마리놀렌산 복합체(DPOC)의 경구투여는 혈청 IgE, IL-4, IL-5를 감소시키는 것으로 나타났으며, 김치로부터 추출한 프로바이오틱스를 아토피 환자에게 섭취시켰을 때 IgE, IL-4, IL-5 감소와 같은 긍정적인 효과를 볼 수 있을 것으로 기대한다. 여러 종류의 프로바이오틱스는 아토피의 증상완화 또는 면역 체계에 미치는 영향과 정확한 메카니즘을 밝히기 위하여 과학적인 연구가 필요한 것으로 사료된다.

• 대한본초학회지
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• 제20권2호
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• pp.35-42
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• 2005

Objective : This study was performed to investigate the effect of oral administration of Oldenlandiae Diffusae Herba (ODH) on eosinophil, immunoglobulin-E and interleukin-4 in the experimental asthma induced by ovalbumin. Methods : Asthma was induced to Balb/c mouse by i.p. injection and aerosol immunization with ovalbumin. It was observed the change of the eosinophil number in the BALF. And, it was observed the change of the concentrations of IL-4 in BALF and splenocyte, IgE in serum by ELISA. Results : 1. The number of eosinophil in BALF was significantly decreased in ODH group copared with control group. 2. Concentration of IL-4 in serum, BALF and splenocyte was significantly decreased in ODH group compared with control group, respectively. 3. Level of IgE in serum was significantly decreased in ODH group compared with control group. Conclusion : We found that the effect of ODH extract in asthma was implicated in reductions of IL-4 released from Th2 cell, and decreases of IgE from plasma cell. These findings suggest that ODH extract can produce anti-asthmatic effect, which may playa role in allergen-induced asthma therapy.

• 대한한의학회지
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• 제24권3호
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• pp.65-71
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• 2003

목적 : 정천탕(定喘湯, JCT)이 IgE/mast cell로 유포되는 천식(喘息)등의 알러지성 질환에 대한 효과를 실험적으로 검증하고자 하였다. 방법 : IgE의 혈중농도와(in vivo) 분비 량을 측정하였으며(in vitro), 알러지 관련 유전자의 발현을 RT-PCR로 검색하였고, JCT의 수용성 복합 추출물이 compound 48/80로 유발되는 mast cell line(IC-2)의 histamine의 방출에 미치는 직접적인 영향을 측정하였다(in vitro). 결과 : 정천탕은 ovalbumin으로 유발시킨 마우스의 혈중 IgE량과 IL-4와 CD-40로 유도시킨 spleen B 임파구의 IgE 생성량도 현저하게 감소시켰다. 또한 INF-r의 발현은 증가시킨 반면, IL-4와 IL-6의 발현과 mast cell의 histamine 방출은 억제하는 것으로 나타났다. 결론 : 정천탕의 항알러지 효과를 실험적으로 확인 할 수 있었으며 임상적으로는 천식등 알러지성 질환에 사용 할 수 있을 것으로 사료된다.

• IMMUNE NETWORK
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• 제2권4호
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• pp.195-201
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• 2002

Background: IgE is closely related to the development of allergies. However, the poor relationship between the specific IgE level and the severity of allergic diseases suggests the possibility of functionally different IgE isoforms. With this in mind, rat basophilic leukemia (RBL)-2H3 activation was analyzed with each type of rat IgE for two parameters, exocytosis and IL-4 mRNA production. RBL-2H3 has been well documented in the rat mucosal mast cell line. Methods: RBL-2H3 cells sensitized with each kind of rat IgE was activated by cross-linking FcRI with B5 (monoclonal anti-rat IgE mouse IgG antibodies). The RBL-2H3 exocytosis was measured by analyzing the ${\beta}$-hexosaminidase level, and the level of IL-4 mRNA synthesis was analyzed using semiquantitative RT-PCR. Rat IgE, which was produced by a parasite infection (REP), was prepared using either Paragonimus westermani metacercariae (REP-PW) or Anisakis simplex third stage larvae (REP-AS). A rat IgE prototype of IR162 was prepared by a peritoneal injection of immunocytoma. Results: The level of exocytosis showed a linear relationship with the rat IgE concentration when REP-PW or REP-AS was applied. However, it exhibited a biphasic response with IR162. In addition, the time course of heating at $56^{\circ}C$ illustrated the similarity between REP-PW and REP-AS, which differed from that of IR162. In contrast, the level of IL-4 mRNA synthesis in the RBL-2H3 cells with IR162 was comparable to that of either REP-PW or REP-AS. Conclusion: These results suggest that functionally different rat IgE isoforms exists in RBL-2H3 exocytosis.

• 대한한방소아과학회지
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• 제21권2호
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• pp.13-34
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• 2007

Objectives The purpose of this study is to examine of the effect of SPAR medicines on the atopy eruption control Methods This experiment is about the expression of IgE, IL-4, IL-6, IL_13, IgM, IgG2a, IgG2b, IgG1 level in serum, and $IFN-{\gamma}$ production by SPAR medicines. We assayed for $CD3e^+/CD69^+$, $CD044^+/CD19^+$ positive cells by flow cytometry in splenocytes and observed the revelation of $CD3e^+/CD69^+$, $CD4^+/CD8^+$, $CD44^+/CD19^+$ marker in PBMC, spleen and DLN. We also observed the outturn of IL-4, IL-5, CCR3, $IFN-{\gamma}$ in skin of a NC/Nga mice. We also analyzed NC/Nga mice's ear and neck-back skin after biopsy and dye by H&E staining method, measured about epidermis and dermis part in comparison with control group. Results SPAR medicines as treatment result to a NC/Nga mice, clinical skin severity score decreased remarkably than the ontrol group. Specially, experiment was results by measuring IgE and IL-6 content in serum 8 weeks, 10 weeks, 12 weeks, 16 weeks, 20 weeks respectively, and it was decreased remarkably than the control group. After experiment ended, the result that observed the revelation CD3e, CD4, CD8, CD19, CD69, CD11a marker in lymph node establishment were observed and that B/T rate becomes recover as normal with political background. In addition to that, the control group was decreased in the measured value of IL-4, IL-5, IL-13, IgM, IgG2a, IgG1's level in serum, and $IFN-{\gamma}$' production secreted in Th1 cell displayed increase by SPAR medicines. IL-4, IL-5, CCR3, and $IFN-{\gamma}$'s gene revelation amount displayed marked decrease than the control group in result that observe effect that get in skin of a NC/Nga dermatitis mouse. Moreover in culture supernatant which cultivate for 14 days after separate skin cell, IL-13 and IL-6 production, and $CD69^+/CD3e^+$, $CD44^+/CD19^+$ expression cell number was decreased than the control group's number. Course inflammation immunocyte permeated of result that effect that SPAR medicines get to NC/Nga mice's skin establishment analyzes ear and neck-back skin after biopsy, and dye by H&E method decreased about epidermis and inflammation of dermis part remarkably than the control group. Conclusions Th1 cell and Th2 cell observe to be shifted by secretion amount of IL-4 and $IFN-{\gamma}$ by SPAR medicines could know that SPAR medicines can be use for treatung allergy autoimmune disease.