• Biomolecules & Therapeutics
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• 제30권6호
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• pp.520-528
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• 2022

Mast cells are an effector cell that plays a pivotal role in type I hypersensitive immune responses. Mast cells exist in connective tissues, such as skin and mucosal tissue, and contain granules which contain bioactive substances such as histamine and heparin in cells. The granules of mast cells are secreted by antigen stimulation to cause the type I allergic hypersensitivity. In addition, stimulated by antigen, mast cells synthesize and secrete various eicosanoids and cytokines. While AT9283 is known to have anticancer effects, the therapeutic effect of AT9283 on allergic disorders is completely unknown. In this study, it was found that AT9283 reversibly inhibited antigen-IgE binding-induced degranulation in mast cells (IC₅₀, approx. 0.58 μM) and suppressed the secretion of the inflammatory cytokines IL-4 (IC₅₀, approx. 0.09 μM) and TNF-α (IC₅₀, approx. 0.19 μM). For a mechanism of mast cell inhibition, while not inhibiting Syk phosphorylation, AT9283 suppressed the activation of LAT, a downstream substrate protein of Syk, in a dose-dependent manner. As expected, AT9283 also inhibited the activation of PLCγ1 and Akt, downstream signaling molecules of Syk/LAT, and MAP kinases such as JNK, Erk1/2, and P38. In an in vitro protein tyrosine kinase assay, AT9283 directly inhibited Syk activity. Next, AT9283 dose-dependently inhibited passive cutaneous anaphylaxis (PCA), an IgE-mediated allergic acute response, in mice (ED50, approx. 34 mg/kg, p.o.). These findings suggest that AT9283 has potential to use as a new drug for alleviating the symptoms of IgE-mediated allergic disorders.

• 동의생리병리학회지
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• 제17권2호
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• pp.428-435
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• 2003

This research was performed to examine an anti-inflammatory effects of Gamisangryosamul-Tang(GSS) and anti-pruritus effects of Ziyang-Go(Salve). This study was processed by three experiments; Experiment 1: Inhibitory activity of GSS extract on the degranulation of mast cell and histamine release in plasma induced by compound 48/80 i.p, injection after the pretreatment of GSS extract i.p, injection in Sprague-Dawley rats, Experiment 2: Anti-inflammatory effect of GSS extract on macropharge raw 264,7 cells treated by LPS 250 ppm (before 2 hours). Experiment 3: Measurement of passive cutaneous anaphylaxis and atopic dermatitis using NC/Nga mice, GSS extract inhibited histamine release by 70% compared to compound 48/80 treated control group and histologically significantly reduced (P<0,01) the degranulation of mast cell in SD rats. In GSS extract treated group, the expression of TNF-α in macropharge cell showed the remarkable inhibitory effect about 62% (P<0,01) compared to LPS treated control group. The expression of IL-6 appeared more effective by 46% than the LPS treated control group and by 6% compared to hydrocortison treated group, Comparing with steroid (0.05% prednisolon) ointment, Ziyan-Go treated group showed the significant(30%) recovery on skin response index in atopic dermatis like anaphylaxis mice(NC/Nga), Finally, in scratching behavioral tests of NC/Nga mice for three weeks, Ziyang-Go treated group significantly (P<0.05) suppressed the pruritus on the face, neck, ears and dorsal skin than inbred NC/Nga mice. However, the change of IgE and IFN-γ from the spleen cell of NC/Nga mice was not significantly different between the oral intake of GSS extract group and of saline intaked control group. Summary and Conclusion: This study demons trates that Ziyang-go have the equal anti-pruritus effect to steroid ointment and GSS extract have the notable immunologic activity on inflammatory in vivo and in vitro model. Advanced experiment of this study will be required for more reliable information about the correlation between the lymphokine (i.e. IgE) and the anti-allergic effects of GSS.

• Advances in Traditional Medicine
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• 제9권2호
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• pp.115-127
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• 2009

Samsoeum (SSE) is used in traditional oriental medicine for various medicinal purposes. However, the exact mechanism that accounts for the anti-allergy and anti-inflammatory effects of the SSE is still not fully understood. The aim of the present study is to elucidate whether and how SSE modulates the allergic reactions in vivo, and inflammatory reaction in vitro. In this study, we showed that SSE significantly decreased compound 48/80-induced systemic anaphylaxis, ear-swelling response, histamine release from preparation of rat peritoneal mast cells and anti-dinitropheny IgE-induced passive cutaneous reaction. Also, SSE inhibited the expression of inflammatory cytokine and cyclooxygenase-2 in PMA plus A23187-stimulated human mast cells (HMC-1). In addition, we showed that anti-inflammatory mechanism of SSE is through suppression of nuclear factor-${\kappa}B$ activation and $I{\kappa}B-{\alpha}$ phosphorylation/degradation in HMC-1. These results provided new insight into the pharmacological actions of SSE as a potential molecule for therapy of inflammatory allergic diseases.

• 셀메드
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• 제8권1호
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• pp.5.1-5.4
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• 2018

Pharmacopuncture, or herbal acupuncture, is a new form of therapy derived from combinations of two traditional therapeutic methods, herbal medicine and acupuncture therapy. To compare the efficacy between loratadine-pharmacopuncture (LP) and loratadine-oral administration (LO), the effect of loratadine was investigated in murine models. Anti-anaphylactic effects of loratadine treatments were investigated in compound 48/80-induced systemic anaphylactic reaction and passive cutaneous anaphylaxis (PCA). LP treatment significantly inhibited the compound 48/80-induced systemic anaphylactic reaction and PCA. The effect between LP and LO were on a similar level. These results indicate that LP can be used as an alternative method for LO in case of emergency.

• 동의생리병리학회지
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• 제16권2호
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• pp.239-244
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• 2002

Okbyungpoongsan-Gami (OG) has been used for the treatment of excessive sweating with general weakness and allergic rhinitis recently. Anal therapy is another way of taking Oriental medicine. It is an important pathway but not available in common clinical situation. This experiment was performed in order to study the inhibitory effect of immediate-type allergic reaction of OG by anal therapy. In addition, the experiment was practised by 1 H-NMR spectroscopy to examine molecular structure of OG. The results were obtained as follows : OG concentration-dependently inhibited compound 48/80- induced immediate type systemic allergic reaction with concentrations of 0.01-1.0g/kg by anal administration 1 h before injection of compound 48/80. OG also concentration-dependently inhibited compound 48/80- induced ear swelling response with concentrations of 0.01-1g/kg by anal administration 1h before injection of compound 48/80. OG also inhibited the passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody concentration- dependently at concentrations ranging from 0.01 to 1g/kg. When OG was pretreated at concentrations ranging from 0.01 to 1g/ℓ, the histamine release from the rat peritoneal mast cells induced by compound 48/80 was reduced in a concentration-dependent manner. OG (0.1-1g/ℓ) had a significant inhibitory effect on histamine release from IgE-induced activated mast cells. OG is seen to be a biochemical compound certainly by 1 H-NMR spectroscopy According to above results, anal therapy of OG may be beneficial in the treatment of systemic and local immediate-type allergic reactions by inhibition of histamine release from mast cells.

• 식품산업과 영양
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• 제9권1호
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• pp.36-45
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• 2004

Bamboo salt has been used for the purpose of prevention and treatment of various diseases in Korea. Present study was carried out to ascertain the effects of purple bamboo salt upon anti-allergic effect, anti-inflammatory activity and immune-enhance effect as well. Purple bamboo salt significantly inhibited the ear swelling response and histamine release induced by compound 48/80 in mice and rat peritoneal mast cells. Purple bamboo salt (0.01 ∼ lg/kg) also dose-dependently inhibited the passive cutaneous anaphylaxis by oral administration. Purple bamboo salt (1 mg/mL) in hibited phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$ and IL-6 secretion, by 67.04${\pm}$0.08%, 68.01${\pm}$1.85%, 69.48${\pm}$0.54%, respectively. In addition, purple bamboo salt inhibited the expression of TNF-${\alpha}$ mRNA in HMC-1 cells. Finally, we investigated the effect of purple bamboo salt in the forced swimming test (FST) and the change of purple bamboo salt-mediated cytokine production from MOLT-4 cells. At the 7th, immobility time was significantly decreased in the purple bamboo salt-administration group (35.4 ${\pm}$5.9 s for 1 g/kg) in comparison with the control group (93.2 ${\pm}$ 15.45). After FST, the content of glucose in the blood serum was increased and the levels of blood urea nitrogen, lactic dehydrogenase was decreased in purple bamboo salt-administration group. However, it had no effect on the elevation of CK and TP level. Purple bamboo salt (1 mg/mL) significantly increased the interferon (IFN)-${\gamma}$ and IL-2 level compared with media control (about 3.7-fold for IFN-${\gamma}$, about 3.5-fold for IL-2, p〈0.05) but did not affect the IL-4.

• Parasites, Hosts and Diseases
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• 제34권1호
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• pp.35-48
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• 1996

국내 우점종인 노랑털깔따구(Chironomus flaviplumus) 성충의 조항원을 제조하여 IgE 항체에 관여하는 주 항원 단백질을 찾아내고자 본 연구를 수행하였다 노랑털깔따구 성충의 조항원을 마우스에 $1{\;}\mu\textrm{g}$과 $10{\;}\mu\textrm{g}$으로 각각 3회씩 면역시킨 결과 ELISA와 PCA 반응시험에서 모두 $1{\;}\mu\textrm{g}$ 면 역군 중 9주째 얻은 혈청에서 가장 높은 깔따구-특이-IgE 항체를 얻을 수 있었다. 노랑털깔따구 성충의 조항원을 SDS-PAGE로 전기영동하여 16-18개의 단백질 구획을 얻었고 이를 chemiluminescent substrate를 이용하여 면역이적법을 시행한 결과 65 kDa에서 강한 단백질 구획이 52 35 및 25 kDa에서 약한 단백질 구획이 관찰되었다. 깔따구 조항원을 전기영동한 겔을 30개 절편으로 절단하여 추출한 각각의 단백질 분획을 P-K 피부반응검사한 결과, 65, 52 및 35 kDa 부위에서 강한 양성반응을 보여 항원성이 확인되었고, 25 kDa 부위에서는 약한 반응을 보였다. 면역이적법에서 관찰하지 못한 15 kDa 부위의 단백질에서도 높은 P-Ktiter값을 보여 15 kDa 단백질도 항원성이 있음을 알 수 있었다. 이상의 결과에서 국내 우점종인 노랑털깔따구 성충이 알레르기 질환의 원인 항원으로 작용하며 주항원 단백질은 15, 35, 52 및 65 kDa의 4개이고 이중 65 kDa 단백질이 가장 강한 allergen으로 관찰되었다.

• 한국미생물·생명공학회지
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• 제39권3호
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• pp.266-273
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• 2011

인도산 울금 분말을 bifidobacteria와 lactobacilli를 포함한 프로바이오틱 유산균으로 발효한 시료들의 소염활성 정도를 세포 내 염증성 인자들의 발현양을 관찰함으로써 평가하였다. 그 중 L. johnsonii IDCC 9203으로 발효한 시료의 소염 활성이 가장 뛰어났다. 이를 바탕으로 울금 분말을 포함한 본배양 배지에서 L. johnsonii IDCC 9203으로 21시간 동안 배양 후 얻은 상등액으로 발효 울금 원료를 제조하였고, 제조된 발효 울금 원료에 대한 소염활성 효능을 테스트하기 위해 LPS로 활성화된 raw 264.7 세포주에 처리하고 COX-2와 iNOS의 발현양을 확인하였다. 그 결과 발효 울금 원료 250 ${\mu}g$/mL까지 농도 의존적으로 COX-2와 iNOS의 발현을 감소시켰으며, 그 저해 활성은 동일 농도의 비발효 울금 원료보다 강하였다. NC/Nga 아토피 피부염 동물모델과 PCA 동물모델에서 발효 울금 원료의 효능 확인 결과 대조군에 비해 아토피 피부염의 초기 증상 개선효과와 급작형 과민반응에 대한 예방효과가 뛰어남을 확인하였다. 발효 울금 원료의 유효성분 함량을 분석했을 때 커큐민의 함량은 비발효 울금 원료에 비해 2.5배 증가했으며, 수용성 커큐민의 함량 역시 증가하였다. 또한 비스디메톡시커큐민이나 디메톡시커큐민의 함량도 증가되었을 뿐 아니라 전체 커큐미노이드 중에서 이들 유도체의 비중이 높아짐을 확인하였다. 모든 결과들을 종합하면, 울금 분말을 L. johnsonii IDCC 9203을 이용하여 발효함으로써 유효성분인 커큐미노이드들의 성분비가 변화하고 수용성 커큐미노이드의 증가에 의한 생체 이용율 증가로 울금의 소염 및 항알레르기 활성이 증가된다. 본 연구를 통해 L. johnsonii IDCC 9203으로 발효한 울금 원료는 급성기 피부염에 대한 예방 및 치료 목적으로 사용 가능할 것으로 예상된다.

• Journal of Dairy Science and Biotechnology
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• 제21권2호
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• pp.97-104
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• 2003

본 연구에서는 우유 앨러지의 원인물질중의 하나인 casein단백질을 생체가 알르겐 물질로 인식할 수 없는 수준의 분자로까지 분해하여 항원성을 저감시키고 또한 풍미가 좋은casein분해물을 제조하기 위하여 분해특성이 다른 효소를 사용하여 만들어진 분해물의 특성과 항원성을 조사하였다. 박테리아 효소인 Neutrase, Alcalase, Protamex, Pescalase을 처리한 casein가수분해물의 평균분자량은 1,100~2,300 dalton이었고 곰팡이 효소인 MP, Flavourzyme, LP, Promod경우에는 거의 770 ~ 1,140 dalton범위였다. 항원성 저감정도를 측정하기 위하여 토끼항casein항혈청을 이용하여 ELISA억제시험을 실시한 결과 항체결합을 50%저해하는 미분해casein단백질의 농도는 $10^{3.6}$ng/ml였다. 박테리아 효소인 Neutrase, Alcalase, Protamex, Pescalase에 의한 Casein가수분해물의 값은 각각 $10^{4.8},\;10^{5.5},\;10^{5.9},\;10^{6.1}\;ng/ml$이었고, 곰팡이 효소인 MP, Flavourzyme, LP, Promod경우에는 각각 $10^{6.3},\;10^{6.3},\;10^{6.5},\;10^{6.8}\;ng/ml$로 나타났다. 박테리아와 곰팡이효소의 조합인 Fla+prota, Pro+prota처리구에서는 $10^{7.4},\;10^{7.3}ng/ml$로 나타났다. 따라서 미분해 casein의 항원성을 1로 하면, casein분해물의 항원성은 최고 1/8,000 이하로 저하되었다. 수신피부아나피랙시스반응(PCA)을 이용한 항원성시험에서 casein으로 피하 감작할 경우 푸른색 반점이 나타났으나 효소처리구에서는 이러한 반점이 나타나지 않아 충분히 항원성이 저감화 되었음을 확인하였다.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.456-464
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• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.