Mast Cell-mediated Allergic Reactions Research Articles

Mosla punctulata Inhibits Mast Cell-mediated Allergic Reactions Through the Inhibition of Histamine Release and Inflammatory Cytokine Production.

Allergic inflammatory diseases such as food allergy, asthma, sinusitis and atopic dermatitis are increasing worldwide. This study examined the effects of aqueous extract of Mosla punctulata on mast cell-mediated allergic inflammation and studied the possible mechanism of action. Aqueous extract of Mosla punctulata inhibited compound 48/80-induced systemic and immunoglobulin E-mediated local anaphylaxis and it also reduced intracellular calcium level and down-streamed histamine release from mast cells. In addition, aqueous extract of Mosla punctulata decreased gene expression and secretion of tumour necrosis factor alpha, an important proinflammatory cytokine, in mast cells. The inhibitory effect on tumour necrosis factor alpha expression was nuclear factor kappa B dependent. The results indicate that aqueous extract of Mosla punctulata inhibited mast cell-mediated allergic inflammatory reaction by suppressing histamine release and expression of tumour necrosis factor alpha, and involvement of calcium and nuclear factor kappa B in these effects. Hence it can be concluded that, the aqueous extract of Mosla punctulata might be a possible therapeutic candidate for allergic inflammatory disorders.

Zinc Oxide Nanoparticles Demoted MDM2 Expression to Suppress TSLP-Induced Mast Cell Proliferation

Activation of murine double minute 2 (MDM2) through thymic stromal lymphopoietin (TSLP)-induced signal transducers and activators of transcription (STAT6) phosphorylation plays a critical role in proliferation and survival of mast cells. Previously, we reported that zinc oxide nanoparticles (ZnO-NP) effectively decrease the mast cell-mediated allergic inflammatory reactions. Here, we evaluated the effect of ZnO-NP on TSLP-induced proliferation of mast cells. ZnO-NP significantly reduced the number of BrdU-incorporating mast cells increased by TSLP. ZnO-NP decreased the expression of MDM2 through the blockade of STAT6 phosphorylation. TSLP increased the production and mRNA expression of interleukin-13 (a growth factor of mast cells), its increase was significantly decreased by ZnO-NP (10 μg/mL). ZnO-NP induced the down-regulation of Bcl2 (an anti-apoptotic factor) and up-regulation of Bax (an apoptotic factor) through the stabilization of p53 protein. However, ZnO-NP has no effect on caspase-3 activation, cytochrome c release into cytosol, and apoptosis-inducing factor translocation into nucleus in TSLP-stimulated cells. The results of the present study demonstrated that ZnO-NP inhibited the proliferation of mast cells through the regulation of MDM2 and p53 protein levels. These finding suggest that ZnO-NP could be improved mast cell-mediated various diseases.

R4 Regulator of G Protein Signaling (RGS) Proteins in Inflammation and Immunity.

G protein-coupled receptors (GPCRs) have important functions in both innate and adaptive immunity, with the capacity to bridge interactions between the two arms of the host responses to pathogens through direct recognition of secreted microbial products or the by-products of host cells damaged by pathogen exposure. In the mid-1990s, a large group of intracellular proteins was discovered, the regulator of G protein signaling (RGS) family, whose main, but not exclusive, function appears to be to constrain the intensity and duration of GPCR signaling. The R4/B subfamily--the focus of this review--includes RGS1-5, 8, 13, 16, 18, and 21, which are the smallest RGS proteins in size, with the exception of RGS3. Prominent roles in the trafficking of B and T lymphocytes and macrophages have been described for RGS1, RGS13, and RGS16, while RGS18 appears to control platelet and osteoclast functions. Additional G protein independent functions of RGS13 have been uncovered in gene expression in B lymphocytes and mast cell-mediated allergic reactions. In this review, we discuss potential physiological roles of this RGS protein subfamily, primarily in leukocytes having central roles in immune and inflammatory responses. We also discuss approaches to target RGS proteins therapeutically, which represents a virtually untapped strategy to combat exaggerated immune responses leading to inflammation.

Differential TLR-induced cytokine production by human mast cells is amplified by FcɛRI triggering.

Mast cells are mainly present in strategic locations, where they may have a role in defence against parasites and bacteria. These pathogens can be recognized by mast cells via Toll-like receptors (TLR). Allergic symptoms are often increased in the presence of pathogens at the site of allergen exposure, but it is unknown which cytokines can mediate such an effect. To study whether an interaction between IgE- and TLR-mediated activation of human mast cells can contribute to exacerbated inflammatory responses. Peripheral blood-derived mast cells were stimulated with TLR ligands, in the presence or absence of anti-IgE triggering, after which degranulation was measured using flow cytometry and cytokine production was evaluated by multiplex assays, and ELISA. For evaluation of allergen-specific responses, mast cells were sensitized with serum of allergic individuals or controls, after which they were stimulated using allergens in combination with TLR ligands. Simultaneous triggering of mast cells via IgE and TLR ligands greatly enhanced cytokine production but not IgE-induced degranulation. Different TLR ligands specifically enhanced the differential production of cytokines in conjunction with FcεRI triggering. Importantly, only TLR-4 and TLR-6 were able to induce robust production of IL-13, an important molecule in allergic reactions. These results indicate that the simultaneous presence of pathogen- or danger-associated signals and FcεRI triggering via specific IgE can significantly modify mast cell-mediated allergic reactions via synergistic production of cytokines and inflammatory mediators and provide an explanation of augmented allergic symptoms during infection.

Inhibitory effect of Moutan Cortex aqueous fraction on mast cell-mediated allergic inflammation.

Moutan Cortex and its major compounds have been shown to possess various biological activities, including anti-inflammatory properties. However, the effects of Moutan Cortex aqueous fraction (MCA) and its molecular mechanisms have yet to be elucidated. In this study, we attempted to evaluate the effects of MCA on mast cell-mediated allergy inflammation in vitro and in vivo compared with major Moutan Cortex compounds. Thus, we examined the anti-inflammatory effects of a water extract of Moutan Cortex by comparing the inhibition of β-hexosaminadase and tumor necrosis factor-α (TNF-α) release in an aqueous fraction with other major compounds of Moutan Cortex. The inhibitory mechanism of MCA was investigated by western blotting in IgE-mediated DNP-BSA-stimulated RBL-2H3 cells. We confirmed the pharmacological effects of MCA on compound 48/80-induced allergic reactions in a mouse model by assessing scratching behavior and passive cutaneous anaphylaxis (PCA)-like reaction. Consequently, MCA inhibited IgE-mediated DNP-BSA-induced β-hexosaminadase and TNF-α release via inactivation of p38, ERK, Akt, and NF-κB in RBL-2H3 cells. MCA reduced compound 48/80-induced PCA reaction and scratching behavior in mice. This inhibitory effect of MCA is more potent than major compounds of Moutan Cortex. In conclusion, our results suggest that MCA has more potential in the treatment of allergic inflammatory diseases compared to other major compounds of Moutan Cortex.

TSLP Induces Mast Cell Development and Aggravates Allergic Reactions through the Activation of MDM2 and STAT6

Thymic stromal lymphopoietin (TSLP) is known to promote T helper type 2 cell-associated inflammation. Mast cells are major effector cells in allergic inflammatory responses. We noted that the population and maturation of mast cells were reduced in TSLP-deficient mice (TSLP-/-). Thus, we hypothesized that TSLP might affect mast cell development. We found that TSLP induced the proliferation and differentiation of mast cells from bone marrow progenitors. TSLP-induced mast cell proliferation was abolished by depletion of mouse double minute 2 (MDM2) and signal transducers and activators of transcription 6 (STAT6), as an upstream activator of MDM2. TSLP-/-, in particular, had a considerable deficit in the expression of MDM2 and STAT6. Also, the TSLP deficiency attenuated mast cell-mediated allergic reactions through the downregulation of STAT6 and MDM2. In an antibody microarray chip analysis, MDM2 expression was increased in atopic dermatitis patients. These observations indicate that TSLP is a factor for mast cell development, and that it aggravates mast cell-mediated immune responses.

케어스웰을 이용한 사이토카인 억제 효과에 대한 연구

Objectives : In this study, we attempted to evaluate the effects of Careswell on human mast cell-mediated allergy inflammation in vitro and pruritogen-induced scratching behavior in vivo. Method : The Careswell was extract by distilled water. The anti-itching effects of Careswell were investigated on the compound 48/80 (<TEX>$50{\mu}g/kg$</TEX>) or histamine (<TEX>$100{\mu}g/kg$</TEX>) induced scratching behavior male ICR mice for 30 min by an observer blind. Terfenadine (10 mg/kg) was used as a positive control drug. The cell toxicity of Careswell was determined by 3-(4,5-dimethylthiazole-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The regulatory effect of Careswell on interleukin (IL)-6 and tumor necrosis factor (TNF)-<TEX>${\alpha}$</TEX> levels was determined by enzyme-linked immunosorbent assay (ELISA) in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) stimulated human mast cells (HMC-1). Also, we evaluated the effect of Careswell on PMACI induced the activation of Nuclear factor-kappa B (NF-<TEX>${\kappa}B$</TEX>) into nucleus by Western blot analysis. Result : The results revealed that the oral administration of Careswell (200 mg/kg, p.o.) attenuated the compound 48/80 or histamine-induced scratching behavior in mice. We showed that Careswell significantly reduced the PMACI-induced the production of IL-6 (0.5-1 mg/ml) and TNF-<TEX>${\alpha}$</TEX> (0.1-1 mg/ml). Additionally, Careswell significantly inhibited the activation of NF-<TEX>${\kappa}B$</TEX> in PMACI-stimulated HMC-1. Conclusion : Collectively, the findings of this study provide us with a novel insight into the pharmacological actions of Careswell as a potential molecule for use in the treatment of allergic inflammation diseases.

Zinc oxide nanoparticles, a novel candidate for the treatment of allergic inflammatory diseases

Zinc (Zn) is an essential trace metal for eukaryotes. The roles of Zn in the numerous physiological functions have been elucidated. Bamboo salt contains Zn that was shown to have anti-inflammatory effect and other health benefits. Nanoparticles of various types have found application in the biology, medicine, and physics. Here we synthesized tetrapod-like, zinc oxide nanoparticles (ZO-NP; diameter 200nm, source of Zn) using a radio frequency thermal plasma system and investigated its effects on mast cell-mediated allergic inflammatory reactions. ZO-NP was found to inhibit the productions and mRNA expressions of inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α on the phorbol 12-myristate 13-acetate plus A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells. In these stimulated cells, caspase-1 and nuclear factor-κB activations were abolished by ZO-NP, and the expressions of receptor interacting protein2 (RIP2) and IκB kinaseβ (IKKβ) induced by PAMCI were reduced. On the other hand, ZO-NP alone increased the expressions of RIP2 and IKKβ in normal condition. ZO-NP inhibited the phosphorylation of extracellular signal-regulated protein kinase in the PMACI-stimulated HMC-1 cells. Furthermore, ZO-NP significantly inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. These findings indicate that ZO-NP effectively ameliorates mast cell-mediated allergic inflammatory reaction, and suggest that ZO-NP be considered a potential therapeutic for the treatment of mast cell-mediated allergic diseases.

6]-Shogaol inhibits the production of proinflammatory cytokines via regulation of NF-κB and phosphorylation of JNK in HMC-1 cells

[6]-Shogaol is a major bioactive component of Zingiber officinale. Although [6]-shogaol has a number of pharmacological activities including antipyretic, analgesic, antitussive and anti-inflammatory effects, the specific mechanisms of its anti-allergic effects have not been studied. In this study, we present the effects of [6]-shogaol on mast cell-mediated allergic reactions in vivo and in vitro. Sprague–Dawley rats received intradermal injections of anti-DNP IgE was injected into dorsal skin sites. After 48 h, [6]-shogaol was administered orally 1 h prior to challenge with DNP-HSA in saline containing 4% Evans blue through the dorsal vein of the penis. In addition, rat peritoneal mast cells (RPMCs) were cultured and purified to investigate histamine release. In vitro, we evaluated the regulatory effects of [6]-shogaol on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionomycin A23187-stimulated human mast cells (HMC-1). [6]-Shogaol reduced the passive cutaneous anaphylaxis reaction compared to the control group, and histamine release decreased significantly following the treatment of RPMCs with [6]-shogaol. In HMC-1 cells, [6]-shogaol inhibited the production of TNF-α, IL-6 and IL-8, as well as the activation of nuclear factor-κB (NF-κB) and phosphorylation of JNK in compound 48/80-induced HMC-1 cells. [6]-shogaol inhibited mast cell-mediated allergic reactions by inhibiting the release of histamine and the production of proinflammatory cytokines with the involvement of regulation of NF-κB and phosphorylation of JNK.

Role of Adaptor Molecule Gab2 in Mast Cell-mediated Allergy Response

Mast cells are major players in allergic responses. IgE-dependent activation through Fc epsilon RI leads to degranulation and cytokine production, both of which require Gab2. To clarify how the signals diverge at Gab2, we established Gab2 knock-in mice that express Gab2 mutated at either the PI-3K- or SHP-2-binding sites. Examination of these mutants showed that both binding sites were required for the degranulation and anaphylaxis response, but not for cytokine production or contact hypersensitivity. Furthermore, the PI-3K- but not the SHP-2-binding site was important for granule translocation during degranulation. We also identified a small GTPase, ARF1, as the downstream target of PI-3K that regulates granule translocation. Fc epsilon RI-stimulation induced ARF1 activation, and this response was dependent on Fyn and the PI-3K-binding site of Gab2. ARF1 activity was required for the Fc epsilon RI-mediated granule translocation. These results indicate that Fyn/Gab2/PI-3K/ARF1-mediated signaling is specifically involved in granule translocation and the anaphylaxis response. In this review, I discussed how Gab2 controls biological events especially for mast cell degranulation and allergy response.

율피추출물의 사람 비만세포주 사이토카인 발현 억제 효과

Objectives : Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous inflammtion of the skin. The chestnut inner shell extracts (CI) has been used as a cosmetic material for a long time in Korea. However, the precise anti-allergy effects of CI have yet to be clearly elucidated. In this study, we attempted to evaluate the effect of CI on mast cell-mediated allergy inflammation. Methods : To find the anti-allergy and inflammatory effect of CI, we investigated the inhibitory effect of CI on the production of inflammatory mediators using by enzyme-linked immunosorbent assay in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187) stimulated-human mast cell (HMC-1). Results : In this study, we found that CI did not show cytotoxic effect at up to 10 ug/ml on HMC-1. CI inhibited the production of tumor necrosis factor (TNF)-<TEX>${\alpha}$</TEX>, interleukin (IL)-6 and IL-8 in stimulated HMC-1. Maximal rate of TNF-<TEX>${\alpha}$</TEX>, IL-6 and IL-8 inhibition by CI (10 ug/ml) were about 47.6%, 44.1% and 22.5% respectively. In addition, we showed that Fr.3 isolated from n-Butyl alcohol layer of CI attenuated the production of TNF-<TEX>${\alpha}$</TEX>, IL-6 and IL-8 in HMC-1. Conclusion : Taken together, the findings of this study provide us with a novel insight action of CI as a potential molecule for use in the treatment of allergic inflammation diseases.

Inhibitory Effects of BiRyuChe-Bang on Mast Cell-Mediated Allergic Reactions and Inflammatory Cytokines Production

BiRyuChe-bang (BRC) is a Korean prescription medicine, which has been used to treat allergic rhinitis at Kyung Hee Medical Center. In this work, we investigated the effects of BRC on mast cell-mediated allergic reactions and inflammatory cytokines production, and identified the active component of BRC. Histamine release was measured from rat peritoneal mast cells (RPMCs). Ear swelling and passive cutaneous anaphylaxis (PCA) were examined in mouse models. Phorbol 12-myristate 13-acetate (PMA) plus A23187-induced inflammatory cytokines production was measured using enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used for the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. Activation of nuclear factor (NF)-κB was analyzed by Western blotting. BRC significantly inhibited the compound 48/80-induced ear swelling response, histamine release from RPMCs, PCA activated by anti-dinitrophenyl IgE, and PMA plus A23187-induced inflammatory cytokines production (p < 0.05). In addition, BRC dose-dependently inhibited the mRNA expressions of TNF-α, IL-6, and IL-8 as well as the activation of NF-κB in a human mast cell line, HMC-1 cells. BRC inhibited the levels of TNF-α and IL-6 in mice induced with PCA. Several components of BRC, such as 1,8-Cineole, Linalool, Linalyl acetate, α-Pinene, and α-Terpineol, significantly inhibited the release of histamine from RPMCs (p < 0.05). Among these components, Linalyl acetate was the most effective for inhibiting histamine release. These results indicate that BRC has a potential regulatory effect on allergic and inflammatory reactions mediated by mast cells.

New Knowledge from Past Decade: Role of Zinc in Immune System

Zinc (Zn) is essential for normal cell structure and physiology. Its deficiency causes growth retardation, neuronal degeneration, and immunodeficiency. Zn homeostasis is tightly controlled through Zn transporters and metallothioneins, which regulate Zn concentration and Zn distribution in individual cells, and contributes to Zn-binding protein in cells. Although many molecules involved in these processes have Zn-binding motifs, the molecular mechanisms underlying the role of Zn in the immune system have not been clarified. Recently, we and other groups have demonstrated that Zn plays diverse and specific roles in vivo and in vitro, in studies on the genetic knockout of Zn transporter functions. In this review, we discuss the impact of Zn on mast cell-mediated allergy and T cell-mediated immune responses. We also describe Zn dysregulation as a leading health problem in allergy and immune responses.

Inula japonica extract inhibits mast cell-mediated allergic reaction and mast cell activation

Ethnopharmacological relevanceThe flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of bronchitis, digestive disorders, and inflammation. However, the mechanisms underlying its anti-inflammatory effects remain yet to be elucidated. The objectives of this study were 1) to assess the anti-allergic activity of the ethanol extract of flowers of Inula japonica extract (IFE) in vivo, 2) to investigate the mechanism of its action on mast cells in vitro, and 3) to identify its major phytochemical compositions. Materials and methodsThe anti-allergic activity of IFE was evaluated using mouse bone marrow-derived mast cells (BMMCs) in vitro and a passive cutaneous anaphylaxis (PCA) animal model in vivo. The effects of IFE on mast cell activation were evaluated in terms of degranulation, eicosanoid generation, Ca2+ influx, and immunoblotting of various signaling molecules. ResultsIFE inhibited degranulation and the generation of eicosanoids (PGD2 and LTC4) in stem cell factor (SCF)-stimulated BMMCs. Biochemical analysis of the SCF-mediated signaling pathways demonstrated that IFE inhibited the activation of multiple downstream signaling processes including mobilization of intracellular Ca2+ and phosphorylation of the mitogen-activated protein kinases (MAPKs), PLCγ1, and cPLA2 pathways. When administered orally, IFE attenuated the mast cell-mediated PCA reaction in IgE-sensitized mice. Its major phytochemical composition included three sesquiterpenes, 1-O-acetylbritannilactone, britanin and tomentosin. ConclusionsThis study suggests that IFE modulates eicosanoids generation and degranulation through the suppression of SCF-mediated signaling pathways that would be beneficial for the prevention of allergic inflammatory diseases. Anti-allergic activity of IFE may be in part attributed particularly to the presence of britanin and tomentosin as major components evidenced by a HPLC analysis.

Antiallergic effect of KOB03, a polyherbal medicine, on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse and human mast cells

Ethnopharmacological relevanceKOB03 is a polyherbal medicine consisting of five different herbs and has commonly been used for the treatment of various allergic diseases. However, its precise anti-allergic effect and mechanism remain unknown. Aim of the studyThe aim of this study was to investigate the effect of KOB03 on allergic responses through the regulation of mast-cell mediated allergic inflammation. Materials and methodsTo determine the effect of KOB03 on mast cell-mediated allergic reactions, we investigated the parameter changes of in vivo models such as compound 48/80-induced systemic anaphylaxis and ovalbumin (OVA)-induced allergic rhinitis, and the release of allergic inflammatory mediators such as histamine, immunoglobulin (Ig) E, and inflammatory cytokines via the MAPKs and NF-kappaB pathways. ResultsThe oral administration of KOB03 at doses of 100 and 200mg/kg inhibited histamine release and mortality in compound 48/80-induced anaphylactic rats. KOB03 also improved rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and decreased the serum levels of histamine, OVA-specific IgE and TNF-α in OVA-induced allergic rhinitis in mice. In vitro, KOB03 suppressed compound 48/80-induced histamine release by blocking mast cell degranulation. In addition, KOB03 inhibited the production of inflammatory cytokines such as TNF-α, IL-1β, IL-6 and IL-8 in PMA/A23187-stimulated HMC-1 mast cells by suppressing their gene expression and blocking the ERK1/2 and p38 MAPK and NF-κB pathways. ConclusionsThese results suggest that KOB03 has an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis.

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.

甘松香 (감송향)이 아토피樣 (양) 피부염에 미치는 영향

Objectives NJ is being used to treat inflammatory diseases in Korea. In this study, we attempted to evaluate the effects of NJ on atopic dermatitis (AD)-like lesions and mast cell-mediated allergy inflammation in vivo and in vitro. Methods and Results We investigated to ascertain the pharmacological effects of NJ on 2,4-dinitrofluorobenzene (DNFB)-induced allergic reactions under in vivo conditions. Additionally, to find possible explanations for the anti-inflammatory mechanisms of NJ, we evaluated the regulatory effects of NJ on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). Conclusions NJ inhibited the production of the inflammatory cytokines (IgE, IL-6, IL-8 and TNF-<TEX>${\alpha}$</TEX>) significantly in vivo and in vitro.

Effects of KOB03, a polyherbal medicine in mast cell-mediated allergic response in ovalbumin-induced allergic rhinitis in vivo model and RBL-2H3 mast cells. (177.14)

Abstract KOB03 is a polyherbal medicine originating from Korean Traditional Medicine, which has been clinically applied for the treatment of allergic diseases. Here, we investigated the inhibitory effects of KOB03 on mast cell-mediated allergic responses on ovalbumin-induced allergic rhinitis in guinea pigs and RBL-2H3 mast cells. To determine the effect of KOB03 on mast cell-mediated allergic reactions, we investigated the parameter changes on ovalbumin (OVA)-induced allergic rhinitis in guinea pigs, and the release of allergic inflammatory mediators such as histamine, IgE and inflammatory cytokines in DNP-IgE-stimulated RBL-2H3 mast cells. The oral administration of KOB03 at doses of 200 and 500 mg/kg in OVA-sensitized/challenged guinea pig significantly decreased the serum levels of OVA-specific IgE, histamineand TNF-alpha KOB03 also inhibited the histopathological changes of nasal mucosa with the infilteration of eosinophils and inflammatory cells. Furthermore, KOB03 significantly inhibited DNP-IgE-induced release of histamine in RBL-2H3 cells via suppressing the ERK1/2 phosphorylation. These data suggest that KOB03 has an anti-allergic activity by modulating mast cell-mediated allergic responses.

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.

Effects of Angelica acutiloba on mast cell-mediated allergic reactions in vitro and in vivo

The root of Angelica acutiloba is a widely used herbal medicine which has been used as a typical therapeutic for allergic diseases in traditional medicine. This study was aimed to investigate the effects of A. acutiloba on allergic reactions in in vitro and in vivo models and its mechanism of action. A. acutiloba was extracted by maceration with 80% ethanol (AAE) and standardized by high-performance liquid chromatography. We investigated the effect of AAE on phorbol-12-myristate-13-acetate plus calcium ionophore A23187 (PMACI)-induced cytokine release; phosphorylation of JNK, ERK, and p38 in human mast cell-1 (HMC-1); and compound 48/80-induced release of histamine in rat peritoneal mast cells (RPMCs). We also investigated the effects on Evans blue (EB) extravasation induced by anti-DNP IgE in rats. Treatment with 1, 10 and 100 μg/ml AAE concentration-dependently inhibited the release of cytokines (tumor necrosis factor-α, interleukin (IL) -6, and IL-8) and phosphorylation of ERK and JNK induced by PMACI in HMC-1 cells, but it did not inhibit the phosphorylation of p38. It also inhibited compound 48/80-induced histamine release in RPMCs. Oral administration of 271 mg/kg AAE inhibited EB extravasation in a passive cutaneous anaphylaxis rat model. In conclusion, AAE inhibited mast cell-derived allergic reactions by inhibiting the release of histamine, the production of pro-inflammatory cytokines, and the phosphorylation of ERK and JNK.