• Tuberculosis and Respiratory Diseases
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• 제44권3호
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• pp.601-610
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• 1997

연구배경 : 그람음성 간균의 내독소에 의한 sepsis syndrome에서 단핵 식세포는 내독소에 의해 자극받아 여러 종류의 cytokine을 분비함으로써 개체를 방어하는데 있어 매우 중요한 역할을 한다. 그러나 불행히도 cytokine들은 개체를 방어하는 작용 뿐 아니라 TNF등의 경우처럼 심각한 조직손상을 가져오는 효과도 있다. 그러므로 생체 내에서 내독소에 반응하여 cytokine의 분비를 조절하는 기능은 매우 중요하다. 이전의 연구에서 미리 내독소에 노출된 단색 식세포는 내독소로 재자극 시 cytokine 생성능의 저하가 관찰되었는데 이러한 현상을 '내독소 내성'이라고 하며 cytokine 분비조절에 중요한 역할을 하리라 생각되나 그 기전 등에 대해서는 연구가 부족한 상태이다. 방 법 : 생체 외에서 내독소에 대한 내성획득의 조건을 확립하고자 정상인의 말초혈액 단핵구를 10ng/ml의 저농도 내독소로 24시간 전처치한 후 2회 세척하고 다시 1 ng/ml의 내독소로 각각 4시간, 6시간, 24시간 자극하여 TNF-$\alpha$와 IL-8의 단백량을 측정하고 총 RNA를 분비하였다. 내독소 내성 획득 기전을 밝히고자 내독소 전처치 시에 자가혈청, PMA, antiCD14 Ab, Indomethacin, $PGF_2$를 각각 첨가하여 내성획득에 영향을 주는지 알아보았다. TNF-$\alpha$와 IL-8의 단백량은 ELISA를 이용하여 측정하였고 분리한 RNA를 이용하여 TNF-$\alpha$와 IL-8에 대한 Northern blot analysis를 시행하였다. 결 과 : 말초혈액을 저농도 내독소로 전처치하면 TNF-$\alpha$ 단백 생성 및 mRNA 발현을 억제하였으나 IL-8에 대해서는 이러한 현상을 관찰할 수 없었다. 전처치 시에 antiCD14 Ab를 내독소와 같이 준 경우 억제된 TNF-$\alpha$ 생성이 부분적으로 회복되었다. PMA만으로 전처치 하여도 저농도 내독소 전처치와 유사하게 내독소 내성을 유도할 수 있었다. 결 론 : 내독소에 의한 내성획득에는 CD14가 관여하고 Protein kinase C 경로를 통하며 pretranslational 수준에서 조절되는 것으로 생각된다.

• 대한한의학회지
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• 제22권4호
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• pp.10-21
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• 2001

Objective : To investigate the effect between Fructus Immaturus Ponciri (FIP, the immature fruit of Poncirus trifoliata) and Fructus Ponciri (FP, the ripe fruit of Poncirus trifoliata) on mast cell-mediated immediate-type allergic reactions. Methods : We performed anaphylactic reaction, histamine release, cAMP, $TNF-{\alpha}$, IgE. Results : The aqueous extract of FIP dose-dependently inhibited systemic and local allergic reaction was induced by compound 48/80 or anti-dinitrophenyl (DNP) IgE in a murine model. FIP also significantly inhibited mast cell-dependent ear swelling response induced by topical application of compound 48/80. When mice were orally pretreated with FIP, the plasma histamine levels were reduced in a dose-dependent manner. FIP dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMCs) was activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMCs, when FIP was added, increased compared with that of a normal or control. In addition, FIP had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-a ($TNF-{\alpha}$) production from the RPMCs and IgE produced by lipopolysaccharide-stimulated murine whole spleen cells or U266B1 as human IgE-bearing B cells. However, FP showed the lower inhibition rate than those of FIP in above all allergic reactions. Conclusion : These data have important implications for our understanding of the clinical effects of FIP and FP on allergic diseases, and FIP is more effective than FP on the allergic reaction.

• 생명과학회지
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• 제21권12호
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• pp.1721-1725
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• 2011

현재 전 세계적으로 알러지 질환은 급격히 증가하고 있는 추세이다. 기존의 길항제나 항원 특이적 면역 치료법의 부작용으로 인하여 항 알러지 작용에 효과적인 천연 기능성 물질에 대한 연구가 알러지 질환 치료의 유망한 분야로 여겨지고 있다. 비만세포는 히스타민이나 아라키돈 산, 그리고 전 염증성 사이토카인 등을 방출하는 알러지 반응에 주요하게 작용하는 효과세포이다. 우리는 참당귀의 뿌리로부터 추출한 노다케닌의 알러지 반응 억제효과에 대해서 연구하였다. 노다케닌을 이용하여 비만세포에서의 탈 과립현상 억제 효과를 측정한 결과, 비만세포에서 노다케닌이 탈과립의 표지인 ${\beta}$-hexosaminidase의 방출량을 농도 의존적으로 억제하는 것을 관찰하였고, 이러한 탈과립 억제 현상이 다양한 사이토카인 중 IL-4과 TNF-${\alpha}$의 양을 감소시킴으로써 매개된다는 사실을 RT-PCR을 통해 확인하였다. 또한 쥐에서 수동피부과민반응을 유도하여 노다케닌을 경구투여 했을 때 알러지성 과민반응 증상을 효과적으로 억제하는 것을 관찰하였다. 결과적으로, 이러한 결과들은 노다케닌이 항 알러지 약물의 개발에 잠재적인 후보물질이 될 수 있음을 시사한다.

• 동의생리병리학회지
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• 제26권6호
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• pp.902-907
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• 2012

The worldwide prevalence and severity of allergic diseases including atopic dermatitis and asthma has increased dramatically over the past decade, especially in developed countries. Mast cells are important effector cells in allergic reactions. The purpose of this study was undertaken to investigate the anti-allergic activities of the extract of Duchesnea chrysantha (DCE). DCE was prepared by extracting with 80% ethanol. In the present study, we investigate the effect of DCE on the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, IL-8, and histamine in the human mast cell line (HMC-1 cells) and on the scratching behavior in hairless mice. Various concentrations of DCE were treated before the activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187. PMA plus A23187 significantly increased TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and IL-8 production compared with media control. We also show that the increased cytokines such as TNF-${\alpha}$ IL-$1{\beta}$, IL-6, and IL-8 were significantly inhibited by DCE in a dose-dependent manner. Moreover, DCE inhibited the histamine release from HMC-1 cells stimulated by compound 48/80, which promotes histamine release. Futhermore, the administration of DCE reduced the scratching behavior induced by pruritogen (compound 48/80 or histamine) in hairless mice. These results suggest that DCE has a potential use as a medicinal plant for treatment against allergy-related disease.

• 한방안이비인후피부과학회지
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• 제23권1호
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• pp.8-22
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• 2010

Objectives : The purpose of this study is to investigate the effects of Gyejijakyakjimo-Tang on the Allergic Contact Dermatitis caused by 2,4-dinitro-chlorobezene(DNCB). Methods : Twenty eight mice were divided into four groups ; normal, control, experimental group A and B. Control and experimental groups were induced allergic contact dermatitis by DNCB. Experimental group A was orally administered the Gyejijakyakjimo-Tang and experimental group B was orally administered the prednisolone. In this study, ear thickness measurement, auricle microphotograph observation, MPO(Myeloperoxidase) activity measurement, Reverse transcription-polymerase chain reaction(RT-PCR) analysis of the mRNA level of TNF-$\alpha$, IL-$1{\beta}$ were performed on these four groups. In addition, the effect of Gyejijakyakjimo-Tang on cell viability and the effect of Gyejijakyakjimo-Tang on the compound 48/80-induced histamine release from HMC and RPMC were measured. Results: 1. Both experimental group A and B had decreased ear thickness compared with control group In contact hypersensitivity assay. 2. In experimental group A, inflammatory edema was similarly observed comparing to control group. Nevertheless, inflammatory edema was obviously reduced in experimental group B. In both experimental group A and B, pathological lesion of dermatitis were alleviated. In addition, the numbers of infiltrated inflammatory cells were decreased compared with control group. 3. Compared to the normal group, there was a noticeable increase in MPO activity in control group. However, in experimental group A and B, it showed remarkable inhibition of the increase in MPO activity comparing with control group. 4. The level of expression of TNF-$\alpha$, IL-$1{\beta}$ in experimental group A and B were meaningfully lower than those in control group. 5. In MTT assay, the concentrations of Gyejijakyakjimo-Tang that were used on the test had no cytotoxicity. 6. Gyejijakyakjimo-Tang dose-dependently inhibited the compound 48/80-induced histamine release from both HMC and RPMC. Conclusions : According to above experiments, Gyejijakyakjimo-Tang was effective on allergic contact dermatitis.

• Natural Product Sciences
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• 제13권4호
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• pp.283-288
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• 2007

Acanthopanacis Cortex (AC) has been popularly used as an herbal medicine for medical treatment of rheumatoid arthritis, insomnia, impotence and diabetes. Here, we investigated immunostimulating effects of the aqueous extract of AC on macrophage. We studied nitric oxide (NO) and tumor necrosis factor (TNF)-${\alpha}$ release in response to AC treatment, as they are important secretory products of macrophage. AC alone induce the NO and TNF-${\alpha}$ production. AC increase c-Jun NH2-terminal kinase 1/2 (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation but does not p38 activation in RAW 264.7 cells. Also AC resulted in the enhanced cell-surface expression of CD80 and CD14. In addition, AC resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon (IFN)-gamma. After feeding with AC to mouse for 10 days, the change of $CD28^+$ and $CD40^+$ population was analyzed. AC increased $CD28^+$ population in splenocytes in vivo. These studies indicate that AC induces macrophage activation and suggest the possible use of AC in macrophage-based immunotherapies.

• Parasites, Hosts and Diseases
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• 제57권2호
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• pp.201-206
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• 2019

The roles of mast cells in allergic diseases and helminth infections are well known. However, the roles of mast cells in T. gondii infection is poorly understood. This study was focused on the production of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-4), chemokines (CXCL8, MCP-1) and nitric oxide (NO) by mast cells in response to soluble lysate of T. gondii tachyzoites. Production of CXCL8 (IL-8), MCP-1, $TNF-{\alpha}$ and IL-4 were measured by RT-PCR and ELISA. Western blot were used for detection of CXCR-1 and CXCR2. Our results showed that T. gondii lysates triggered mast cells to release CXCL8, MCP-1, $TNF-{\alpha}$, IL-4 and to produce NO. This suggests that mast cells play an important role in inflammatory responses to T. gondii.

• 한국한의학연구원논문집
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• 제16권3호
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• pp.155-166
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• 2010

Objetives : The purpose of this study was to examine the pathway of anti-allergic effects of Aconiti Ciliare Tuber (ACT). Methods : We examined cell viability, ${\beta}$-hexosaminidase release, pro-inflammatory cytokines secretion and mRNA expressions, nuclear factor-kappa B (NF-${\kappa}B$) (p65) activation, inhibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) degradation, and MAPKs activation from RBL-2H3 cells pre-treatment by ACT of 1.0 mg/ml, 2.0 mg/ml separately. Results : We observed that ACT reduced the secretion of ${\beta}$-hexosaminidase, TNF-${\alpha}$, IL-4 and the expression of COX-2 mRNA in RBL-2H3 cells. Futhermore, ACT inhibited the levels of activation of NF-${\kappa}B$ (p65) protein, ERK MAPK, and degradation of $I{\kappa}B-{\alpha}$ in RBL-2H3 cells. Conclusions : These results show that ACT has an anti-histamine effect and inhibitory effect of NF-${\kappa}B$ (p65) through regulation of $I{\kappa}B-{\alpha}$ degradation. This improves that ACT could be used as an anti-allergic medicine.

• 대한한방소아과학회지
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• 제24권1호
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• pp.93-103
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• 2010

Objectives The purpose of this study was to examine the pathway of anti-allergic effects of Cheonmaec-tang (CMT). Methods We examined the cell viability, $\beta$-hexosaminidase release, pro-inflammatory cytokines secretion and mRNA expressions, nuclear factor-kappa B (NF-${\kappa}B$) (p65) activation, inbibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) degradation, and MAPKs activation in RBL-2H3 cells pre-treated by CMT of 2.0 mg/ml, 4.0 mg/ml separately. Results We observed that CMT reduced the secretion of $\beta$-hexosaminidase, TNF-$\alpha$, IL-4 and the expression of COX-2 mRNA in RBL-2H3 cells. Furthermore, CMT inhibited the levels of activation of NF-${\kappa}B$ (p65) protein, ERK MAPK, and degradation of $I{\kappa}B-{\alpha}$ in RBL-2H3 cells. Conclusions These results show that CMT has an anti-histamine effect and inhibitory effect of NF-${\kappa}B$ (p65) through regulation of $I{\kappa}B-{\alpha}$ degradation. These suggest that CMT could be used as an anti-allergic medicine.

• BMB Reports
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• 제38권6호
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• pp.639-645
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• 2005

Protein kinase C (PKC) isozymes, a family of serine-threonine kinases, are important regulators of cell proliferation and malignant transformation. Phorbol esters, the prototype PKC activators, cause PKC translocation to the plasma membrane in prostate cancer cells, and trigger an apoptotic response. Studies in recent years have determined that each member of the PKC family exerts different effects on apoptotic or survival pathways. $PKC{\delta}$, one of the novel PKCs, is a key player of the apoptotic response via the activation of the p38 MAPK pathway. Studies using RNAi revealed that depletion of $PKC{\delta}$ totally abolishes the apoptotic effect of the phorbol ester PMA. Activation of the classical $PKC{\alpha}$ promotes the dephosphorylation and inactivation of the survival kinase Akt. Studies have assigned a pro-survival role to $PKC{\varepsilon}$, but the function of this PKC isozyme remains controversial. Recently, it has been determined that the PKC apoptotic effect in androgen-dependent prostate cancer cells is mediated by the autocrine secretion of death factors. $PKC{\delta}$ stimulates the release of $TNF{\alpha}$ from the plasma membrane, and blockade of $TNF{\alpha}$ secretion or $TNF{\alpha}$ receptors abrogates the apoptotic response of PMA. Molecular analysis indicates the requirement of the extrinsic apoptotic cascade via the activation of death receptors and caspase-8. Dissecting the pathways downstream of PKC isozymes represents a major challenge to understanding the molecular basis of phorbol ester-induced apoptosis.