• IMMUNE NETWORK
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• v.9 no.6
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• pp.274-284
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• 2009

Background: Swiprosin-1 was identified in human CD8+ lymphocytes, mature B cells and non-lymphonoid tissue. We have recently reported that swiprosin-1 is expressed in mast cells and up-regulated in both in vitro and in vivo. Methods: The expression of cytokines and swiprosin-1 were determined by by real time PCR and conventional PCR. Pharmacological inhibitors were treated to investigate potential mechanism of swiprosin-1 in mast cell activation. Actin content was evaluated by confocal microscopy and flow cytometry. Results: The swiprosin-1 augmented PMA/A23187-induced expression of cytokines and release of histamine. However, knock-down of swiprosin-1 showed only a modest effect on PMA/A23187-induced cytokine expression, suggesting that swiprosin-1 has gain-of-function characteristics. Swiprosin-1 was found in microvilli-like membrane protrusions and highly co-localized with F-actin. Importantly, either disruption of actin by cytochalasin B or inhibition of PI3 kinase, an enzyme involved in actin remodeling, by wortmannin blocked cytokine expression only in swiprosin-1-overexpressing cells. Conclusion: These results suggest that swiprosin-1 modulates mast cell activation potentially through actin regulation.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.159-166
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• 2004

Objective : Mast cells are a potent source of mediators that regulate inflammatory response in allergies and asthma. The author studied the effect of Bojungikgitanggamibang(BITB) on mast cell-mediated anaphylactic reaction. Method : When BITB was given as pre-treatment at concentrations ranging from 0.01 to 1 mg/ml, the histamine release from rat peritoneal mast cells induced by compound 48/80 was reduced in a dose-dependent manner. Result : BITB dose-dependently inhibited compound 48/80-induced systemic anaphylactic shock. BITB also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. In addition, BITB inhibited phorbol 12-myristate 13-acetate and A23187-induced interleukin-6 secretion from human mast cell line HMC-1 cells. Conclusion : These results indicate that BITB may be actively anti-allergic.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.11 no.1
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• pp.40-53
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• 1998

Mast cells play an important role in the pathophysiologlcal changes observed in acute cutaneous and inflammatory diseases In order to see whether Kum-Hwang-San has an influence on mast cell- mediated immediate cutaneous reactions, the author has undertaken an animal study. Ears of mice were treated with a compound 48/80 solution topically at 30 min after the cutaneous application of Kum-Hwang-San. At each point, an ear swelling response was measured with a digimatic thickness micrometer. Ear swelling response induced by compound 48/80 was significantly suppressed dose-dependently by Kum-Hwang-San 30 min before topical application as compared with that in nonapplicated control mice, and the value returned to normal levels by 120 min. Compound 48/80- induced mast cell degranulation by Kum-Hwang-San was also remarkably decreased in accordance with the suppression in ear swelling response. Kum-Hwang-San dose-dependently inhibited histamine release from the rat peritoneal mast cells activated by compound 48/80. Another way to test acute cutaneous reaction is to induce passive cutaneous anaphylactic reaction. Kum-Hwang-San significantly inhibited passive cutaneous anaphylactic reaction activated by anti-dinitrophenyl IgE on both topical application and intradermal injection. Kum-Hwang-San also inhibited histamine release from the rat peritoneal mast cells induced by anti-DNP IgE. This study provides evidence that Kum-Hwang-San will be beneficial in the treatment of acute cutaneous diseases.

• Advances in Traditional Medicine
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• v.3 no.2
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• pp.56-62
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• 2003

The effect of aqueous extract of Terminalia chebula fruit (Combretaceae) (TCAE) by anal administration on mast cell-dependent immediate-type anaphylactic reactions was investigated. TCAE (0.005 to 1 g/kg) inhibited systemic anaphylaxis induced by compound 48/80 in mice. When TCAE was pretreated at the same concentrations with systemic anaphylaxis, the plasma histamine levels were reduced in a dose-dependent manner. TCAE (0.1 and 1 g/kg) also significantly inhibited local anaphylaxis activated by anti-DNP IgE. TCAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. Moreover, TCAE (0.01 and 0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$ production from RPMC. These results provide evidence that anal therapy of TCAE may be beneficial in the treatment of systemic and local mast cell-dependent anaphylaxis.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.550-560
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• 2022

Background: The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediated anaphylaxis. Methods: Asthma model was established for evaluating airway changes and ear allergy. RPMCs and RBL-2H3 were used for in vitro experiments. Calcium uptake, histamine release and degranulation were detected. ELISA and Western blot measured cytokine and protein levels, respectively. Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-α, IL-4, IL-8, IL-1β and the degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lung tissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmatic mice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the ear thickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histamine release and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1β, TNF-α, IL-8, and IL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation of mast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in a dose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCγ2, PI3K ERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-κB, AKT-Nrf2, and p38MAPK-Nrf2 pathways. However, G-Rh2 up-regulated Keap-1 expression. Meanwhile, G-Rh2 reduced the levels of p-AKT, p38MAPK and Nrf2 in RBL-2H3 sensitized IgE cells and inhibited NF-κB signaling pathway activation by activating the AKT-Nrf2 and p38MAPK-Nrf2 pathways. Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by the AKT-Nrf2/NF-kB and p38MAPK-Nrf2/NF-κB signaling pathways.

• Biomolecules & Therapeutics
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• v.30 no.6
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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.

• Natural Product Sciences
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• v.10 no.1
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• pp.24-28
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• 2004

The effects of aqueous extract of Artemisia iwayomogi (Compositae) (AIAE) on the mast cell-dependent allergic and inflammatory reactions were investigated. AIAE (0.05 to 1 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80 in mice. AIAE (0.1 and 1 g/kg) also significantly inhibited local allergic reaction activated by anti-DNP IgE. AIAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80. Moreover, AIAE inhibited the secretion of interleukin (IL)-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.

• The Journal of Korean Medicine
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• v.18 no.2
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• pp.167-186
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• 1997

The inhibitory activity of Aquillariae Lignum (Thymelaeaceae) on type Ⅰ immediate hypersensitivity of the anaphylactic type in the wistar rat model of passive cutaneous anaphylaxis, an IgE-mediated, mast cell-dependent reaction. Administered orally at 250, 500 mg/kg body weight 1 h before the challenge, Aquillariae Lignum potently inhibited PCA in rats which disodium cromoglycate showed poor inhibitory activity. Aquillariae Lignum inhibited compound 48/80-induced anaphylaxis 100% with a dose of 0.5 g/kg body weight at 1 h before or 5 and 10 min after injection of compound 48/80. Aquillariae Lignum (0.05-1.6 mg/ml) also exhibited the dose-related inhibitory effect on compound 48/80-induced histamine release from rat_peritoneal mast cells. Moreover, it was clearly demonstrated that Aquillariae Lignum and disodium cromoglycate disodium cromoglycate potently inhibited such type Ⅰ allergic reactions as anaphylactic shocks, suggesting that these drugs, at least in part, share the same mechanism of action It is suggested that Aquillariae Lignum may exert a stronger inhibition on the mast cell degranulation process. Since Aquillariae Lignum (1.0 mg/ml) inhibited about 90% of histidine decarboxylase activity, the inhibitory activity of Aquillariae Lignum for histamine release was considered to be derived from the inhibition of histidine decarboxylase activity. It results from increased expression of the mRNA coding for histidine decarboxylase, as assessed by Northern blot analysis after a 12 h incubation to P-815 cells with dexamethasone plus 12-O-tetradecanoylphorbol-13-acetate. The addition of Aquillariae Lignum to P-815 cells with dexamethasone plus 12-O-tetradecanoyl-phorbol-13-acetate, significantly inhibited the histidine decarboxylase gene expression. Tumor necrosis $factor-{\alpha}$ was not constitutively expressed in P-815 cells. Substance P selectively activates the tumor necrosis $factor-{\alpha}$ gene expression in P-815 cells. Aquillariae Lignurm inhibited substance P-induced tumor necrosis $factor-{\alpha}$ gene expression. Furthennore, The effect of Aquillariae Lignum on the mRNA expression of novel protein kinase C ${\delta}$ a major isoform of mast cells, was examined by Northern blot analysis. The expression of novel protein kinase C ${\delta}$ mRNA in the presence of Aquillariae Lignum was significantly lower than in the absence of Aquillariae Lignum. These results suggest the possibility that the inhibition of allergic reaction by Aquillanae Lignum should be regulated by tumor necrosis $factor-{\alpha}$ and novel protein kinase C ${\delta}$.

• Applied Microscopy
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• v.40 no.4
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• pp.201-209
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• 2010

Korean traditional herbs, especially Anemarrhena asphodeloides (A. asphodeloides), Salvia miltiorrhiza (S. miltiorrhiza), and Terminalia chebula (T. chebula) have been known to have the immunomodulatory, anti-tumor, and anti-inflammatory effects. However, direct cellular mechanism underlying the mast cell-mediated anaphylaxis-like reaction has poorly been understood. In the present study, the effects of the methanol extracts of A. asphodeloides (MEAA), S. miltiorrhiza (MESM), and T. chebula (METC) on anaphylactic reaction were investigated. Using in vitro and in vivo experiments, the influences of MEAA, MESM, and METC on the compound 48/80-induced anaphylaxis-like reaction and mast cell activation, and IgEmediated PCA were examined. Results are below; 1) MEAA, MESM, and METC significantly inhibited systemic anaphylaxis-like reaction, ear swelling response, and IgE-mediated PCA. 2) the compound 48/80-induced mast cell degranulation, histamine release of rat peritoneal mast cells (RPMC) were significantly inhibited by the pretreatment with MEAA, MESM, and METC, and 3) the compound 48/80-induced calcium influx in RPMC was significantly inhibited by the pretreatment with MEAA, MESM, and METC. These results suggest that MEAA, MESM, and METC may be an activity to inhibit the compound 48/80-induced or anti-DNP IgE-mediated anaphylactic reactions by blocking histamine release and calcium uptake into RPMC. MEAA, MESM, and METC potentially may serve as an effective therapeutic tool for allergic diseases.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.79-84
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• 2004

02PS15 extracts (BuOH, $H_2O$, and crude extracts) significantly inhibited IL-4 and IL-6 secretion from the phytohemagglutinin (PHA)-plus phorbol 12-myristate 13-acetate (PMA)-induced peripheral blood mononuclear cleas (P<0.05). 02PS15 extracts (BuOH and crude extracts) also significantly inhibited the histamine release from rat peritoneal mast cells (P<0.05). Significant reduced levels (P<0.05) of PMA- and A23187-induced IL-8 were observed in the human mast cell line, HMC-1, with O2PS15 extracts (BuOH and crude extracts). 02PS15 extracts (BuOH and crude extract) downregulated the expression of IL-6 and IL-8 in the activated HMC-1. These results suggest that O2PS15 has the inhibitory effect of atopic allergic reaction anil this might be useful for clinical application to treat several allergic diseases such as atopic dermatitis.