• Korean Journal of Medicinal Crop Science
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• v.18 no.6
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• pp.398-404
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• 2010

Complementary and alternative medicines are considered as a promising research field to develop new therapies for various allergic diseases. In this study, we investigated the anti-allergic effect of Agrimonia pilosa Ledeb (AP) by using passive cutaneous anaphylaxis in mice and its mechanism of action in mast cells. The extract of AP reversibly inhibited degranulation in RBL-2H3 cells and bone marrow-derived mast cells (BMMCs). AP also suppressed the passive cutaneous anaphylaxis inducing by IgE and antigen (Ag) in a dose-dependent manner. In the study to find its mechanism of action, AP inhibited the phosphorylation of Syk kinase, a pivotal protein which is regulated by Src-family kinase for activation of mast cells. In addition, AP also suppressed activation of Akt and Erk1/2 that are critical for the production of cytokines in mast cells. The results strongly suggest that AP exerts anti-allergic activity in vitro and in vivo through the inhibition of activation of Syk in mast cells.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.251-260
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• 1998

Cromakalim (BRL 34915), known as an airway smooth muscle relaxant, inhibited the releases of mediators in the antigen-induced mast cell activation. It has been suggested that cromakalim, in part, inhibited mediator releases by inhibiting the initial increase of 1,2-diacylglycerol (DAG) produced by the activation of the other phospholipase system which is different from phosphatidylcholine-phospholipase D pathway. The aim of this study is to further examine the inhibitory mechanism of cromakalim on the mediator release in the mast cell activation. Guinea pig lung mast cells were purified by using enzyme digestion and percoll density gradient. In purified mast cells prelabeled with $[^3H]PIP_2$, phospholipase C (PLC) activity was assessed by the production of $[^3H]$insitol phosphates. Protein kinase C (PKC) activity was assessed by measuring the protein phosphorylated from mast cells prelabeled with $[{\gamma}-32P]ATP$, and Phospholipase $A_2\;(PLA_2)$ activity by measuring the lyso-phosphatidylcholine produced from mast cell prelabeled with 1-palmitoyl-2-arachidonyl $phosphatidyl-[^{14}C]choline$. Histamine was assayed by fluorometric analyzer, and leukotrienes by radioimmunoassay. The PLC activity was increased by activation of the passively sensitized mast cells. This increased PLC activity was decreased by cromakalim pretreatment. The PKC activity increased by the activation of the passively sensitized mast cells was decreased by calphostin C, staurosporine and cromakalim, respectively. The $PLA_2$ activity was increased in the activated mast cells. The pretreatment of cromakalim did not significantly decrease $PLA_2$ activity. These data show that cromakalim inhibits histamine release by continuously inhibiting signal transduction processes which is mediated via PLC pathway during mast cell activation, but that cromakalim does not affect $PLA_2$ activity related to leukotriene release.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.232-237
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• 2005

Mast cells play an important role in allergic inflammation by releasing their bioactive mediators. The function of mast cells is enhanced by stimulation because of the induction of specific genes and their products. While many inducible genes have been elucidated, we speculated that a significant number of genes remain to be identified. Thus, we applied differential display (dd) PCR to establish a profile of the induced genes in bone marrow-derived mast cells (BMMCs) after they were co-cultured with 3T3 fibroblasts. To date, 150 cDNA fragments from the connective-type mast cells (CTMCs) were amplified. Among them, thirty cDNA fragments were reamplified for cloning and sequencing. The ddPCR strategy revealed that serine proteases were the most abundant genes among the sequenced clones induced during the maturation. Additionally, unknown genes from the co-culture of BMMCs with 3T3 fibroblasts were identified. We confirmed their induction in the CTMCs by Northern blot analysis and RT-PCR. Characterization of these induced genes during the maturation processes will provide insight into the functions of mast cells.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.259-272
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• 1988

Type I allergic reaction and it's related clinical manifestations are known to occur by the effects of various chemical mediators. These chemical mediators are released from circulating basophils and tissue mast cells, which become 'sensitized' through the binding of antigens and antibodies of the IgE type to their cell surface receptors. Efforts to elucidate the mechanism of the release of these mediators, especially that of histamine, have been persued for years. The mechanism is not yet clarified at the present time. Recent reports of hyaluronidase, an enzyme known to be involved in the tissue inflammatory process, as possible participant in type I allergic reaction, initiated this study. Relationships between the hyaluronidase activity and histamine release from the sensitized rat peritoneal mast cells were investigated. Also anti-allergic agents, tranilast and disodium cromoglycate, along with known histamine releasers, morphine and compound 48/80, were used to observe the inhibitory and stimulatory effects of these substances on the hyaluronidase activity as well as histamine release from the rat mast cells. The results obtained are summarized as follows: 1) Hyaluronidase activity and histamine release from sensitiaed rat peritoneal mast cells started to increase on the 4th day of postsensitization. Hyaluronidase activity reached it's peak value on the 7th day of postsensitization and that of histamine release on the 14th day of postsensitization. 2) Hyaluronidase activity and histamine release from sensitized rat peritoneal mast cells, pre-treated with tranilast revealed significant decrease in comparison with those of non-treated cells. 3) Hyaluronidase activity and histamine release from sensitized rat peritoneal mast cells, pre-treated with tranilast, followed by morphine injection, revealed significant increase in comparison with those of tranilast treated cells. 4) In vitro study of hyaluronidase activity and histamine release from un-sensitized rat peritoneal mast cells, using morphine and compound 48/80 as activators, revealed significant increase compared to those of non-activator used cells. 5) In vitro study of hyaluronidase activity and histamine release from un-sensitized rat peritoneal mast cells, pre-treated with tranilast and disodium cromoglycate, using confound 48/80 and morphine as activators revealed significant decrease in comparison with those of tranilast and disodium cromoglycate treated cells. From above results, participation of enzyme hyaluronidase in the process of histamine release from sensitized rat pertioneal mast cells, could be suggested. It was also quite evident that the clinically used anti-allergic agents, tranilast and disodium cromoglycate, have significant inhibitory function on the hyaluronidase activity and histamine release from sensitized rat peritoneal mast cells, while morphine significantly increased the hyaluronidase activity and histamine release from sensitized rat peritoneal mast cells.

• Korean Journal of Medicinal Crop Science
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• v.16 no.1
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• pp.27-32
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• 2008

This study aimed to investigate the anti-allergic activity and the mechanism of action of Crassirhizomae rhizoma (CR). The extract of CR exhibited potent inhibitory activity in mast cells; its $IC_{50}$ values were $31.2{\pm}1.5{\mu}g/m{\ell}$ for rat basophile leukemia (RBL)-2H3 mast cells and $51.5{\pm}2.1{\mu}g/m{\ell}$ for bone marrow-derived mast cells by antigen stimulation. It also suppressed the expression of TNF-${\alpha}$ and IL-4 mRNAs in RBL-2H3 cells. In an in-vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis (PCA), in a dose-dependent manner. With regard to the mechanism of action, CR inhibited the activating phosphorylation of Syk kinase, a key signaling protein for the activation of mast cells. Taken together, these results strongly suggested that the anti-allergic activity of CR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk in mast cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.673-676
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• 2016

Background: In the maxillofacial region, giant cell granulomas occur in 2 clinical forms, central and peripheral. Despite histopathological similarity between these 2 forms totally different clinical behaviors have been reported. The present study was undertaken to compare mast cell and vascular concentrations in these pathologic lesions. Materials and Methods: In this cross-sectional descriptive study, 20 pathological samples of central giant cell granuloma (CGCG) and 20 samples of peripheral giant cell granuloma (PGCG) were selected and examined through toluidine blue staining for mast cell assessment and immunohistochemical staining by VEGEF antibody for comparing the number of mast cells. T-test, chi-squared test and backward multivariate linear regression were used for statistical analysis using SPSS 20. Statistical significance was set at P<0.05. Results: This study showed significantly greater VEGF expression and mast cell concentrations in CGCG compared to PGCG cases. Also there was a significant correlation between VEGF expression and the concentration of mast cells. No relation was found between age, sex and site of the lesion and concentration of mast cells or VEGF expression. Conclusions: It is feasible that higher concentrations of mast cells in CGCG versus PGCG samples might lead to more aggressive clinical behavior via vascular proliferation and angiogenesis. However, other biologic mechanisms should be considered in this situation.

• Proceedings of the Korean Society of Toxicology Conference
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• 1997.05a
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• pp.65-74
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• 1997

By using guinea pig lung mast cells, this study aimed to examine the effects of Aloe component(NY945) on the mediator releases caused by mast cell activation, and also aimed to assess the effects of NY945 on the mechanism of mediator releases in the mast cell activation. We partially purified mast cells from guinea pig lung tissues by using the enzyme digestion, the rough and the discontinuous density percoll gradient method. Mast cells were sensitized with $IgG_1$ (anti-OA) and challenged with ovalbumin. Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay The phospholipase D activity was assessed more directly by the production of labeled phosphatidylethanol or phosphatidylbutanol which was produced by phospholipase D-mediated transphosphatidylation in the presence of ethanol or butanol. The amount of mass 1,2-diacylglycerol was measured by the [$^3H$]1,2-diacylgycerol produced when prelabeled with [$^3H$]myristic acid. In the mast cells prelabeled with L-[$^3H$]methyl methionine the phospholipid methylation was assessed by measuring the incorporation of the [$^3H$]methyl moiety into phospholipids. Pretreatment of NY945(10$\mu$g) significantly decreased histamine and leukotrienes releases during mast cell activation. The decrease of histamine release was stronger than that of leukotrienes during mast cell activation. The phospholipase D activity increased by the mast cell activation was decreased by the dose-dependent manner in the pretreatment of NY945. The amount of mass 1,2-diacylglycerol produced by activation of mast cells were decreased in the pretreatment of NY945. NY945 pretreatment strongly inhibited the incorporation of the [$^3H$]methyl moiety into phospholipids. The data suggest that NY945 purified from Aloe inhibits in part an increase of 1,2-diacylglycerol which is produced by activating mast cells with antigen-antibody complexes which is mediated via phosphatidylcholine-phospholipise D and phosphatidylinositole-phospholipise C systems, and then followed by the inhibition of histamine release. Furthermore, NY945 reduces the phosphatidylcholine production by inhibiting the methyltransfsrase I and II, which decrease the conversion of phosphatidylcholine into arachidonic acid and inhibits the production of leukotrines.

• Korean Journal of Veterinary Research
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• v.31 no.1
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• pp.77-87
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• 1991

In order to know the influence of mast cells on the mammary tumor development, the growth of the mammary carcinoma, the numerical changes and the morphological findings of mast cells appeared in the tumor were microscopically observed in the rat treated with DMBA and each chemical of histamine, heparin, pyrilamine or cimetidine. The results observed were summarized as follows: The tumor induction time that represented the number of days elapsing between the 3rd DMBA administration until a first tumor became $10{\times}10mm$ in diameter was $42.5{\pm}4.7$ days, and the mean number of tumor mass per rat was $3.4{\pm}1.2$ in the DMBA-treated group. No significant difference was apparent in the tumor induction time of the histamine-treated group, heparin-treated group or pyrilamine-treated group compared with the control group, but in the cimetidine-treated group the tumor induction time was $61.8{\pm}10.6$ days (p<0.005). The mean number of tumors per rat was $2.1{\pm}0.9$ in the cimetidine-treated group in contrast to $3.4{\pm}1.3$ in the control group (p<0.005). Numerical changes of mast cells were observed according to the development of DMBA induced mammary tumors that were separated into three major classes of tumors. The numbers of mast cells in all the experimental group were inclined to increase significantly according to the mammary tumor development (p<0.005), and the histamine-treated group, heparin-treated group, or pyrilamine-treated group were nearly similar to the control group. But the mast cells in the each stage of tumor development were more numerous in the cimetidine-treated group than in the control group (p<0.005). There were not significant in the numerical changes of mast cells among the experimental groups on each stage of carcinomas separated by early stage, middle stage and late stage. In the morphological characteristics of mast cells, the degranulation was not detectable from the hyperplasia stages to the early stage of carcinoma, but its degranulation was observed at the middle stage of carcinoma. Most mast cells were nearly degranulated at the late stage of carcinoma. The histamine treated group, pyrilamine-treated group and cimetidine treated group did not differ from the control group in morphological changes of mast cells, but the degranulation was shown mild in the heparin-treated group. And the degranulation gave rise to the depletion of intercellular matrix via exocytosis all the experimental group. From above results, it is supposed that mast cells inhibit the tumor development and that the inhibition is not caused by a single-factor, but by a complex activities of mast cell mediators.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.189-198
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• 2015

Background: Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction. Methods: Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells. Results: PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase $A_2$ ($PLA_2$), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, $PLA_2$, and transcription factors (nuclear factor-${\kappa}B$ and activator protein-1). Conclusion: PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the $Ca^{2+}$ influx, protein kinase C, and $PLA_2$, which are propagated by Syk activation upon allergic stimulation of mast cells.

• Journal of Food Hygiene and Safety
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• v.30 no.4
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• pp.376-382
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• 2015

Allergic diseases have rapidly increased in recent years. Mast cells play a critical role in IgE-mediated allergy responses and, therefore, closely associated with rhinitis, asthma, and atopic dermatitis. We studied anti-allergic effect of Penthorum chinense extract (PCE) in vitro and in vivo. PCE inhibited the degranulation of mast cells by antigen stimulation and its effect was dose-dependent and reversible in mast cells. PCE also suppressed the production of inflammatory cytokines such as TNF-${\alpha}$ and IL-4 by antigen in mast cells. Mechanistically, PCE inhibited the activation of Syk/LAT pathway which is a key signaling pathway for the activation of mast cells by antigen. Notably, PCE suppressed IgE-mediated allergic responses by antigen in mice. These results strongly suggest that PCE is a potential candidate for anti-allergic treatment.