Mast Cell-mediated Allergic Inflammation Research Articles

Galangin attenuates mast cell-mediated allergic inflammation

A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. In this study, we investigated anti-allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models. Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells (HMC-1). Galangin decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8. The inhibitory effect of galangin on theses pro-inflammatory cytokines was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1. Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue. The inhibitory effects of galangin were more potent than cromolyn, a known anti-allergic drug. Our results showed that galangin down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines. In light of in vitro and in vivo anti-allergic inflammatory effects, galangin could be a beneficial anti-allergic inflammatory agent.

Piceatannol inhibits mast cell-mediated allergic inflammation

Piceatannol is a phenolic stilbenoid and a metabolite of resveratrol which is found in red wine. Piceatannol (PIC) commonly exhibits anti-inflammatory, antiplatelet and antiproliferative activity. In the present study, the anti-allergic and anti-inflammatory mechanisms of PIC were investigated by examining the effects of PIC on pro‑inflammatory cytokine release and phosphorylation of mitogen-activated protein (MAP) kinases (ERK, JNK and p38) in a human mast cell line. PIC dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated local allergic reactions. PIC reduced the immunoglobulin E (IgE)-mediated local allergic reaction and attenuated histamine release from rat peritoneal mast cells. Histamine and β-hexosaminidase release was markedly decreased dose-dependently by PIC treatment in RBL-2H3 cells. PIC treatments of HMC-1 cells definitely reduced mRNA expression and the release of the pro‑inflammatory cytokines, tumor necrosis factor-α and interleukin-8. MAP kinase phosphorylation was also strongly decreased dose-dependently following PIC treatment. PIC regulated the production of cytokines and histamine in phorbol 12-myristate 13-acetate plus A23187-stimulated mast cells. Thus, PIC may alleviate allergic inflammation and may be a useful therapeutic agent for allergic diseases.

Angelicae Gigantis Radix regulates mast cell-mediated allergic inflammation in vivo and in vitro

Angelicae Gigantis (AG) Radix, commonly used medicinal food, has been reported as a promising candidate for inflammatory diseases. However, the anti-allergic effects of AG and its molecular mechanisms have yet to be clarified. The present study investigated the anti-allergy effects of ethanol extracts of AG on mast cell-mediated allergic inflammation in vivo and in vitro. The finding of this study demonstrated that AG reduced anti-dinitrophenyl IgE antibody-induced passive cutaneous anaphylaxis, compound 48/80-induced histamine release, 2,4-dinitrofluoro benzene-induced contact hypersensitivity. In addition, AG inhibited the production of interleukin (IL)-6, IL-8, and TNF-α, as well as the activation of Jun N-terminal kinase and nuclear factor-κB in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cells. In conclusion, our results provide a novel insight into the pharmacological actions of AG as a potential candidate for use in allergic inflammatory diseases.

Betula platyphylla attenuated mast cell-mediated allergic inflammation in vivo and in vitro

AimsBetula platyphylla (B. platyphylla) has traditionally been used in Korea to treat inflammatory diseases. However, the exact mechanism that accounts for the anti-inflammatory effect of B. platyphylla is not completely understood. The aim of the present study is to elucidate whether and how B. platyphylla modulates the mast cell-mediated allergy inflammation in vitro and in vivo.Main methodsWe investigated to ascertain the pharmacological effects of B. platyphylla on both compound 48/80 or histamine-induced scratching behaviors and 2, 4-dinitrochlrobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of B. platyphylla, we evaluated the effects of B. platyphylla on the release of histamine in compound 48/80-induced rat peritoneal mast cells (RPMCs), production of inflammatory mediators and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1).Key findingsThe finding of this study demonstrated that B. platyphylla reduced compound 48/80 or histamine-induced scratching behaviors and DNFB-induced atopic dermatitis in mice. Additionally, B. platyphylla inhibited the release of histamine in RPMC and production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1.SignificanceCollectively, the findings of this study provide us with novel insights into the pharmacological actions of B. platyphylla as a potential molecule for use in the treatment of allergic inflammatory diseases.

Sparassis crispa suppresses mast cell-mediated allergic inflammation: Role of calcium, mitogen-activated protein kinase and nuclear factor-κB

Allergic inflammatory disease such as food allergy, asthma and atopic dermatitis are increasing worldwide. In this study, we investigated the effect of water extract of Sparassis crispa (WESC) Fr. (Aphyllophoromycetideae) on mast cell-mediated allergic inflammation and the possible mechanisms of action. WESC inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. WESC decreased immunoglobulinE (IgE)-mediated passive cutaneous anaphylaxis. Additionally, WESC reduced histamine release and intracellular calcium in human mast cells activated by phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. WESC decreased PMA and A23187-stimulated expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, inlerleukin (IL)-6 and IL-1β. The inhibitory effect of WESC on pro-inflammatory cytokines was nuclear factor-κB, extracellular signal-regulated kinase and p38 mitogen-activated protein kinase-dependent. Our results suggest potential therapeutic application of WESC in allergic inflammatory diseases.

Perfluorooctanoic acid induces mast cell-mediated allergic inflammation by the release of histamine and inflammatory mediators

Perfluorooctanoic acid (PFOA) has unique physical and chemical characteristics, water and oil repellency, thermal stability, and surfactant properties. PFOA has been regularly found in the blood of animals and humans worldwide, and has become an increasing concern because of its adverse effects in immune system. However, the role of PFOA in the allergic inflammation is not well-known. To further extend the immunotoxicity of PFOA, we examined the role of PFOA on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. PFOA dose- and time-dependently increased histamine release from mast cells and serum histamine by the induction of intracellular calcium. PFOA exacerbated the IgE-dependent local allergic reaction in the mouse allergy model. PFOA induced gene expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in mast cells. The inducing effect of PFOA on the pro-inflammatory cytokines was nuclear factor-κB, p38 mitogen-activated protein kinase, and caspase-1 dependent. Furthermore, the activation of cyclooxygenase-2 by PFOA suggests the induction of allergic inflammatory mediators by the PFOA. Our findings provide evidence that PFOA, the known immunotoxic agent, induces mast cell-derived allergic inflammatory reactions by histamine release and expression of pro-inflammatory cytokines.

Anti-inflammatory effects of low-molecular weight chitosan oligosaccharides in IgE–antigen complex-stimulated RBL-2H3 cells and asthma model mice

The anti-inflammatory effects of low-molecular weight chitosan oligosaccharides (LM-COS) prepared from high-molecular weight chitosan by enzymatic digestion were investigated against allergic reaction and allergic asthma in vivo and in vitro. Allergic asthma is an inflammatory disease of the airways associated with enhanced degranulation and cytokine generation. The LM-COS (<1kDa), consisting of glucosamine (GlcN)n, n=3–5, were capable of inhibiting both antigen-stimulated degranulation and cytokine generation in rat basophilic leukemia RBL-2H3 cells. The protective effect of LM-COS against ovalbumin (OVA)-induced lung inflammation in asthma model mice was also examined. Oral administration of LM-COS (16mg/kg body weight/day) resulted in a significant reduction in both mRNA and protein levels of interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor (TNF)-α in the lung tissue and bronchoalveolar lavage fluid (BALF); The protein levels of IL-4, IL-13 and TNF-α in BALF were decreased by 5.8-fold, 3.0-fold and 9.9-fold, respectively, compared to those in the OVA-sensitized/challenged asthma control group. These results suggest that the oral administration of LM-COS is effective in alleviating the allergic inflammation in vivo and thus can be a good source material for the development of a potent therapeutic agent against mast cell-mediated allergic inflammatory responses and airway inflammation in allergic inflammatory diseases, including asthma.

Aqueous Extract ofMosla chinensisInhibits Mast Cell-Mediated Allergic Inflammation

Allergic inflammatory diseases such as food allergy, asthma, sinusitis, and atopic dermatitis are increasing worldwide. In this study, we investigated the effects of aqueous extract of Mosla chinensis Max. (AMC) on mast cell-mediated allergic inflammation and studied the possible mechanism of this action. AMC inhibited compound 48/80-induced systemic and immunoglobulin E (IgE)-mediated local anaphylaxis. AMC reduced intracellular calcium levels and downstream histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. In addition, AMC decreased gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in human mast cells. The inhibitory effect of AMC on cytokine expression was nuclear factor (NF)-κB dependent. Our results indicate that AMC inhibits mast cell-mediated allergic inflammatory reaction by suppressing histamine release and expression of proinflammatory cytokines and the involvement of calcium and NF-κB in these effects. AMC might be a possible therapeutic candidate for allergic inflammatory disorders.

Ripe fruit of Rubus coreanus inhibits mast cell-mediated allergic inflammation

In this study, we investigated the effect of a water extract of the ripe fruits of Rubus coreanus Miq. (Rosaceae) (RFRC) on mast cell-mediated allergic inflammation and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. RFRC dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. RFRC reduced the immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis. RFRC attenuated histamine release from rat peritoneal mast cells and human mast cells by the reduction of intracellular calcium. RFRC decreased the phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of RFRC on cytokine production was nuclear factor (NF)-κB- and mitogen-activated protein kinase (MAPK)-dependent. In addition, RFRC suppressed the activation of caspase-1. Our findings provide evidence that RFRC inhibits mast cell-derived allergic inflammatory reactions, and for the involvement of calcium, NF-κB, MAPKs and caspase-1 in these effects. Furthermore, in vivo and in vitro anti-allergic inflammatory effects of RFRC provide affirmative proof of a possible therapeutic application of this agent in allergic inflammatory diseases.

Elsholtzia ciliatainhibits mast cell-mediated allergic inflammation: role of calcium, p38 mitogen-activated protein kinase and nuclear factor-κB

Mast cell-mediated allergic reaction is involved in many diseases such as asthma and allergic rhinitis. Therefore, discovery of drugs for the prevention or treatment of allergic disease is an important topic in human health. In this study, we evaluated the effects of water extract of Elsholtzia ciliata (Thunb.) Hyland (Labiatae) (WEEC) on mast cell-mediated allergic inflammation and studied the possible mechanisms of action. WEEC inhibited compound 48/80-induced systemic and immunoglobulin E-mediated local anaphylaxis, and serum histamine release in mice. WEEC reduced intracellular calcium levels and downstream histamine release from human mast cells (HMC-1) activated with phorbol 12-myristate 13-acetate and calcium ionophore A23187. In addition, WEEC decreased gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in HMC-1. The inhibitory effect of WEEC on cytokine expression was nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) dependent. Our results indicate that WEEC inhibits mast cell-mediated allergic inflammatory reactions by suppressing histamine release and proinflammatory cytokine expression, and involvement of calcium, NF-κB and p38 MAPK in these effects.

Genistein-4′-O-α-L-rhamnopyranosyl-(1→2)- β-D-glucopyranoside from Sophora japonica (Leguminosae) ameliorates mast cell-mediated allergic inflammation in vivo and in vitro

Genistein-4′-O-α-L-rhamnopyranosyl-(1–2)- β-D-glucopyranoside (GRG) is one of constituents isolated from Sophora japonica (Leguminosae). It is known to exert various effects such as anti-inflammatory effect. However, the anti-allergic effects of GRG and its molecular mechanisms have yet to be clearly elucidated. In this study, we attempted to evaluate the effects of GRG on mast cell-mediated allergic inflammation in vitro and in vivo. We investigated to ascertain the pharmacological effects of GRG on compound 48/80-induced systemic anaphylaxis and experimental scratching behavior in mice. Additionally, to find a possible explanation for the anti-allergic mechanisms of GRG, we evaluated the regulatory effects of GRG on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that GRG reduced compound 48/80-induced systemic anaphylaxis and scratching behavior in mice. Additionally, GRG inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-8 and histamine as well as the activation of caspase-1 in PMACI-stimulated HMC-1. Taken together, the findings of this study provide a novel insight into the pharmacological actions of GRG as a potential molecule for use in the treatment of allergic inflammation diseases.

C-kit binding properties of hesperidin (a major component of KMP6) as a potential anti-allergic agent.

Accumulation of mast cells can be causally related to several allergic inflammations. Stem cell factor (SCF) as a mast cell chemotaxin induces mast cell migration. To clarify a new effect of Pyeongwee-San extract (KMP6, a drug for indigestion) for the treatment of allergy, we investigated the effects of KMP6 on SCF-induced migration of rat peritoneal mast cells (RPMCs). A molecular docking simulation showed that hesperidin, a major component of KMP6, controls the SCF and c-kit binding by interaction with the active site of the c-kit. KMP6 and hesperidin significantly inhibited SCF-induced migration of RPMCs (P<0.05). The ability of the SCF to enhance morphological alteration and F-actin formation was also abolished by treatment with KMP6 or hesperidin. KMP6 and hesperidin inhibited SCF-induced p38 MAPK activation. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with KMP6 or hesperidin (P<0.05). Our results show for the first time that KMP6 potently regulates SCF-induced migration, p38 MAPK activation and inflammatory cytokines production through hindrance of SCF and c-kit binding in RPMCs. Such modulation may have functional consequences during KMP6 treatment, especially mast cell-mediated allergic inflammation disorders.

Chrysin suppresses mast cell-mediated allergic inflammation: Involvement of calcium, caspase-1 and nuclear factor-κB

A great number of people are suffering from allergic inflammatory diseases such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid contained in propolis, blue passion flower, and fruits. Several studies reported that chrysin has beneficial effects including anti-tumor and anti-oxidant activities. The aim of the present study was to elucidate whether chrysin modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. Chrysin inhibited immediate-type systemic hypersensitivity and serum histamine release. Chrysin attenuated immunoglobulin E-mediated local anaphylaxis. These inhibitory effects of chrysin on the systemic and local allergic reaction were more potent than cromolyn, a known anti-allergic drug. Chrysin reduced histamine release from mast cells. The inhibitory effect of chrysin on the histamine release was mediated by the modulation of intracellular calcium. In addition, chrysin decreased gene expression of pro-inflammatory cytokines such as, tumor necrosis factor-α, IL (interleukin)-1β, IL-4, and IL-6 in mast cells. The inhibitory effect of chrysin on the pro-inflammatory cytokine was nuclear factor-κB and caspase-1 dependent. Our findings provide evidence that chrysin inhibits mast cell-derived allergic inflammatory reactions by blocking histamine release and pro-inflammatory cytokine expression, and suggest the mechanisms of action. Furthermore, in vivo and in vitro anti-allergic inflammatory effect of chrysin suggests a possible therapeutic application of this agent in allergic inflammatory diseases.

Insamhodo-tang, a traditional Korean medicine, regulates mast cell-mediated allergic inflammation in vivo and in vitro

Insamhodo-tang (IHT) has traditionally been used in Korea to treat a variety of diseases, including chronic cough, tuberculosis, and chronic bronchitis. However, the anti-allergic and anti-inflammatory effects of IHT and its molecular mechanisms have yet to be clearly elucidated. In this study, we attempted to evaluate the effects of IHT on mast cell-mediated allergy inflammation in vitro and in vivo. We investigated to ascertain the pharmacological effects of IHT on both compound 48/80-induced and 2,4-dinitrofluorobenzene (DNFB)-induced allergic reactions under in vivo conditions. Additionally, to find a possible explanation for the anti-inflammatory mechanisms of IHT, we evaluated the regulatory effects of IHT on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that IHT reduced compound 48/80-induced systemic anaphylactic shock, DNFB-induced dermatitis, and ear swelling responses in mice. Additionally, IHT inhibited the production of interleukin (IL)-6, IL-8, and TNF-α, as well as the activation of nuclear factor-κB and caspase-1 in PMACI-stimulated HMC-1. Collectively, the findings of this study provide us with a novel insight into the pharmacological actions of IHT as a potential molecule for use in the treatment of allergic inflammation diseases.

Anti-allergic inflammatory activity of the fruit of Prunus persica: Role of calcium and NF-κB

Mast cell-mediated allergic symptoms are involved in many diseases, such as asthma and sinusitis. In this study, we investigated the effect of ethanol extract of fruits of Prunus persica (L) Batsch (FPP) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. FPP dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated local allergic reactions. Histamine releasing from mast cells was reduced by FPP, which was mediated by modulation of intracellular calcium. In addition, FPP attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of FPP on pro-inflammatory cytokines was nuclear factor (NF)-κB dependent. Our findings provide evidence that FPP inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-κB in these effects.

Meoruh wine suppresses mast cell-mediated allergic inflammation

In this study, we investigated the effect of the Meoruh wine (MW), a Korean traditional wine made by the fruits of Vitis amurensis Rupr. (Vitaceae) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma, and atopic dermatitis. MW inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in a dose-dependent manner in mice. MW decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. MW dose-dependently reduced histamine release from human mast cells activated by phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI). The inhibitory effect of MW on histamine release was mediated by suppression of intracellular calcium. In addition, MW attenuated the PMACI-stimulated expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, and IL-8 in human mast cells. The inhibitory effect of MW on these pro-inflammatory cytokines was nuclear factor (NF)-κB dependent. Our findings provide evidence that MW inhibits mast cell-derived allergic inflammatory reactions and involvement of calcium, pro-inflammatory cytokines and NF-κB in these effects.

Clinopodium gracile inhibits mast cell-mediated allergic inflammation: involvement of calcium and nuclear factor-κB

Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of the water extract of Clinopodium gracile Matsum var. multicaule (WECG) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. WECG inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated cutaneous anaphylaxis in a dose-dependent manner. WECG dose-dependently reduced histamine release from rat peritoneal mast cells and human mast cells. The inhibitory effect of WECG on histamine release was mediated by the modulation of intracellular calcium. In addition, WECG attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 in human mast cells. The inhibitory effect of WECG on these proinflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. Our findings provide evidence that WECG inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-kappaB in these effects.

BALB/c mice에서 quercetin의 경구투여가 picryl chloride로 유발된 접촉성 피부 알레르기의 예방에 미치는 영향

본 연구를 통해 BALB/c 마우스에서 quercetin의 경구투여가 PCL로 유도된 접촉성 피부 알레르기의 예방에 미치는 효과에 대해 알아보았다. Quercetin을 투여 농도에 따라 대조군(0 mg/kg), 저용량군(50 mg/kg), 고용량군(100 mg/kg)으로 나누고 8일에 걸쳐 총 8번 경구투여를 실시한 후 알레르기 유발물질인 PCL을 마우스의 양쪽 귀에 감작시켜 접촉성 피부 알레르기를 유발 시켰다. Quercetin의 투여 농도별 ear swelling 변화를 확인한 결과 quercetin을 투여하지 않은 대조군에 비해 quercetin을 투여한 군의 ear swelling 증가폭이 낮게 나타났고, 100 mg/kg (고용량군)에서 농도 유의적으로 ear swelling의 증가폭이 현저히 낮게 나타났다. Quercetin의 투여 농도에 따른 혈청 내 염증성 매개 물질의 농도 변화를 알아보기 위한 IgE 및 histamine level 측정 결과에서 quercetin을 투여하지 않은 대조군에 비해 quercetin을 투여한 50 mg/kg (저용량군), 100 mg/kg (고용량군)에서 낮은 수준의 IgE, histamine 수치가 나왔다. H&E염색과 Toluidine blue stain을 통한 조직병리학적 검사결과에서 quercetin을 투여한 고용량군의 귀 두께가 대조군에 비해 얇게 관찰되었고, 비만세포의 유무를 알아보기 위한 Toluidine blue stain의 결과 대조군에 비해 고용량군에서 적은 수의 비만세포들이 관찰되었다. 따라서 ear swelling과 IgE, histamine level, 조직병리학적 결과를 종합해 봤을 때 식물성 flavonoid 성분인 quercetin은 접촉성 피부 알레르기의 예방에 상당한 효과가 있다고 판단되며, 부작용이 발생하는 기존의 치료제를 대체할 수 있는 후보 물질로써 중요한 가치가 있다고 사료된다. The number of patients with immune- mediated dermatitis such as contact dermatitis is increasing year by year. Allergic contact dermatitis is a complex phenomenon that involves resident epidermal cells, fibroblasts, and endothelial cells, as well as invading leukocytes that interact with each other under the control of a network of cytokines and lipid mediators. It is a cell-mediated immune reaction, which occurs after susceptible individuals are exposed to sensitizing chemicals, and characteristic eczematous reaction is seen at the point of contact with an allergen. In this study, we investigated the allergy prevention effects of quercetin on mast cell-mediated allergic inflammation in BALB/c mice. BALB/c mice were sensitized with 40 <TEX>${\mu}l$</TEX> of 1.5% picryl choloride (PCL) to the left and right ear each. Total serum IgE levels and histamine levels were measured by the sandwich ELISA method using mouse IgE, histamine measuring kit. For histopathological examination, paraffin sections were stained with hematoxylin and eosin(HE) or toluidine blue(TB). Ear swelling responses were much weaker in the high-dose group (100 mg/kg) than the control group (0 mg/kg). The number of mast cells showed a significant decrease in the high-dose group (100 mg/kg) compared to the control group (0 mg/kg). Degranulation of mast cells was also confirmed by Toluidine Blue (TB) staining method. Both total serum IgE and histamine levels were significantly decreased in the high-dose group (100 mg/kg) compared to other groups. These findings suggest a certain relationship between the elevation of IgE, histamine levels and the degranulation of mast cells. These results show that the pharmacological actions of quercetin indicate its potential activity for prevention of allergic inflammatory diseases through the down-regulation of mast cell activation.

Mast cells: makers and breakers of allergic inflammation

Recent findings have developed, changed, challenged and extended the established view of mast cell biology and of their role in inflammation. The purpose of this review is to present and discuss recent research in this area relating to allergic inflammation. Mast cells are traditionally viewed only as IgE-activated histamine-providing effector cells of allergic inflammation. Yet, recent findings also support a role for mast cells in the sensitization to allergens, and early released human mast cell tryptase has been shown to break down IgE, hence breaking the key maker of allergic inflammation. Furthermore, mast cells demonstrate proinflammatory action through nonhistamine and non-IgE-mediated routes. For example, the role of platelet-activating factor in contributing to allergic inflammation and anaphylaxis in mice is now starting to be shown in humans. Most surprisingly, mast cells have also emerged as modulators and downregulators of allergic inflammation. For example, the newly discovered siglec-8 receptor might act as an inhibitor of mast cell degranulation and thus of mast cell-mediated allergic inflammation. Also, mast cell-derived IL-10 is shown to be a modulator of allergic inflammation, demonstrated in a murine model of contact hypersensitivity. Understanding the mast cell's divergent phenotypes based on situation and setting is required to truly discover their role in allergic inflammation.

Anti-inflammatory effect of leaves of Eriobotrya japonica correlating with attenuation of p38 MAPK, ERK, and NF-κB activation in mast cells

Mast cell-mediated allergic inflammation is involved in many diseases such as asthma and sinusitis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 with immune regulatory properties. In the present study, we investigate the effect an unspecified aqueous extract from leaves of Eriobotrya japonica Lindl. (Rosaceae) (LEJL) on the expression of pro-inflammatory cytokines and its possible mechanisms of action in human mast cells (HMC-1). LEJL dose-dependently inhibited phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 (PMACI)-induced gene expression and secretion of TNF-α, IL-6, and IL-8. LEJL attenuated PMACI-induced activation of nuclear factor (NF)-κB, and specifically blocked activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) but not that of c-jun N-terminal kinase. The inhibitory effect of LEJL on the pro-inflammatory cytokines was likely NF-κB, p38 MAPK, and ERK dependent. Our in vitro studies provide evidence that LEJL might contribute to the treatment of mast cell-derived allergic inflammatory diseases.