RESUMO
Grifola frondosa is an edible mushroom consumed as a health food and/or traditional medicine in Asia. However, the anti-allergic effects of G. frondosa are not yet understood. In this study, we demonstrated the effects of G. frondosa extract (GFE) on IgE-mediated allergic responses, using antigen-stimulated RBL-2H3 cells. Three active compounds: ergosterol, 6ß-methoxyergosta-7,22-dien-3ß,5α-diol (MEDD), and 6-oxoergosta-7,22-dien-3ß-ol (6-OXO) were isolated from GFE and shown to inhibit the antigen-induced release of ß-hexosaminidase and histamine. Among the three active components, we focused on ergosterol because of its high content in GFE. Ergosterol inhibited the aggregation of high-affinity IgE receptor (FcεRI), which is the first step in the activation of mast cells and antigen-induced tyrosine phosphorylation. Furthermore, ergosterol suppressed antigen-increased IL-4 and TNF-α mRNA. Taken together, our findings suggest that G. frondosa, including ergosterol and its derivatives as active components, has the potential to be a novel functional food that prevents type I allergies.
Assuntos
Antígenos/imunologia , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Ergosterol/farmacologia , Grifola/química , Mastócitos/efeitos dos fármacos , Receptores de IgE/efeitos dos fármacos , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular , Ergosterol/química , Alimento Funcional , Liberação de Histamina/efeitos dos fármacos , Mastócitos/imunologia , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Receptores de IgE/imunologia , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Houttuynia cordata has been used as a traditional medicine in Korea and is known to have antioxidant, anti-cancer and anti-allergic activities. The precise effect of H. cordata, however, remains unknown. In this study, we investigated the effects of H. cordata water extract (HCWE) on passive cutaneous anaphylaxis (PCA) in mice and on IgE-mediated allergic response in rat mast RBL-2H3 cells. Oral administration of HCWE inhibited IgE-mediated systemic PCA in mice. HCWE also reduced antigen (DNP-BSA)-induced release of beta-hexosaminidase, histamine, and reactive oxygen species in IgE-sensitized RBL-2H3 cells. In addition, HCWE inhibited antigen-induced IL-4 and TNF-alpha production and expression in IgE-sensitized RBL-2H3 cells. HCWE inhibited antigen-induced activation of NF-kappaB and degradation of IkappaB-alpha. To investigate the inhibitory mechanism of HCWE on degranulation and cytokine production, we examined the activation of intracellular FcepsilonRI signaling molecules. HCWE suppressed antigen-induced phosphorylation of Syk, Lyn, LAT, Gab2, and PLC gamma2. Further downstream, antigen-induced phosphorylation of Akt and MAP kinases (ERK1/2 and JNK1/2 but not p38 MAP kinase) were inhibited by HCWE. Taken together, the in vivo/in vitro anti-allergic effect of HCWE suggests possible therapeutic applications of this agent in inflammatory allergic diseases through inhibition of cytokines and multiple events of FcepsilonRI-dependent signaling cascades in mast cells.
Assuntos
Anafilaxia/tratamento farmacológico , Houttuynia/química , Hipersensibilidade/tratamento farmacológico , Imunoglobulina E/fisiologia , Mastócitos/imunologia , Receptores de IgE/efeitos dos fármacos , Animais , Western Blotting , Linhagem Celular , Citocinas/biossíntese , Feminino , Hexosaminidase B/metabolismo , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E/imunologia , Luciferases/genética , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Extratos Vegetais/farmacologia , RNA/biossíntese , RNA/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptores de IgE/genética , Transdução de Sinais/efeitos dos fármacos , Solventes , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Transfecção , ÁguaRESUMO
BACKGROUND: Atmospheric pollution may play a role in the immune response to allergens either directly or by entering the food chain. While particulate platinum group elements (PLGE) emitted by catalytic converters can be considered biologically inert, approximately 10% of these species accumulate in the environment as bioavailable soluble forms. METHODS: We challenged in vitro human immature and mature monocyte-derived dendritic cells with subtoxic concentrations of soluble species of PLGE. Dendritic cells were studied both at baseline and following treatment with Na(2)PtCl(6), Na(2)PdCl(6) or Na(3)RhCl(6). (NH(4))(6)Mo(7)O(24) was included as control. The following end-points were considered: expression of differentiation markers, effectiveness of allergen presentation and Th2 cytokine production by cocultured T lymphocytes, expression of IgE-type I receptor and efficiency of IgE-dependent endocytosis. RESULTS: We found that treatment with PLGE (but not with the control metal) increased costimulatory molecule expression and antigen presentation, amplified IL-5 production by cocultured T lymphocytes, upregulated IgE-type I receptor membrane expression, and augmented IgE-type I receptor-mediated endocytosis. CONCLUSIONS: We conclude that PLGE have an adjuvant-like effect on dendritic cells that can favor and amplify the immune response to allergens.
Assuntos
Apresentação de Antígeno/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Hipersensibilidade/imunologia , Ativação Linfocitária/efeitos dos fármacos , Compostos de Platina/imunologia , Apresentação de Antígeno/imunologia , Antígeno B7-1/efeitos dos fármacos , Antígeno B7-1/imunologia , Antígeno B7-2/efeitos dos fármacos , Antígeno B7-2/imunologia , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/imunologia , Citometria de Fluxo , Humanos , Ativação Linfocitária/imunologia , Material Particulado/efeitos adversos , Material Particulado/imunologia , Receptores de IgE/efeitos dos fármacos , Receptores de IgE/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
The molecular mechanism of how resveratrol inhibits mast cell degranulation was studied by examining its effects on the signaling components of the high affinity IgE receptor (FcepsilonRI) pathway. Resveratrol inhibited mast cell degranulation in a dose-dependent manner and reduced the FcepsilonRI-mediated tyrosine phosphorylation of ERK and PLCgamma1 but not of Syk and PLCgamma2. U-73 122 and PD98059, which are PLC and MEK inhibitors, also had inhibitory effects on mast cell degranulation. These results suggest that FcepsilonRI-mediated tyrosine phosphorylation of PLCgamma1 and ERK could be potential cellular targets of resveratrol for the inhibition of mast cell degranulation.
Assuntos
Degranulação Celular/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Proteínas Tirosina Quinases/efeitos dos fármacos , Receptores de IgE/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Linhagem Celular Tumoral , Mastócitos/fisiologia , Fosforilação/efeitos dos fármacos , Ratos , Resveratrol , Estilbenos/isolamento & purificação , Veratrum/químicaRESUMO
Polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) have been shown to modulate a number of inflammatory disorders. Mast cells play a critical role in the initiation and maintenance of inflammatory responses. However, the effects of PUFAs on mast cell functions have not been fully addressed. We here-in examined the effects of PUFAs on the high affinity IgE receptor (FcepsilonRI)-mediated mast cell activation using RBL-2H3 cells, a rat mast cell line, that were cultured in the medium containing palmitic acid (PA), AA, or the AA analogs mead acid (MA) and eicosapentaenoic acid (EPA). In AA-supplemented cells, the FcepsilonRI-mediated beta-hexosamidase and TNF-alpha release, calcium (Ca(2+)) influx, and some protein tyrosine phosphorylations including Syk and linker for activation of T cells (LAT) were enhanced, whereas, in MA- or PA-supplemented cells, they were not changed when compared with cells cultured in control medium. In EPA-supplemented cells, the enhancements of beta-hexosamidase release and protein tyrosine phosphorylations were observed. Furthermore, in AA- or EPA-supplemented cells, FcepsilonRI-mediated intracellular production of reactive oxygen species (ROS) that is required for the tyrosine phosphorylation of LAT and Ca(2+) influx were enhanced when compared with the other cells. Thus, preincubation of AA or EPA augmented FcepsilonRI-mediated degranulation in mast cells by affecting early events of FcepsilonRI signal transduction, which might be associated with the change of fatty acid composition of the cell membrane and enhanced production of ROS. The results suggest that some PUFAs can modulate FcepsilonRI-mediated mast cell activation and might affect FcepsilonRI/mast cell-mediated inflammation, such as allergic reaction.
Assuntos
Ácido Araquidônico/farmacologia , Ácidos Graxos Insaturados/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Receptores de IgE/metabolismo , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Cálcio/metabolismo , Degranulação Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Citocinas/metabolismo , Ácido Eicosapentaenoico/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Ácido Palmítico/farmacologia , Fosfoproteínas/metabolismo , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptores de IgE/efeitos dos fármacos , Transdução de Sinais , Quinase Syk , Tirosina/metabolismoRESUMO
Taban-Arshan extract decreased expression of T-lymphocyte activation markers, normalized T-cell-mediated immunity, and suppressed increased activity of natural killer receptors during culturing with lymphocytes of patients with atopic bronchial asthma. Taban-Arshan extract normalized activation processes in the B-cell immunity and stimulated expression of receptors of activation-induced apoptosis.
Assuntos
Antiasmáticos/imunologia , Asma/imunologia , Medicina Tradicional Tibetana , Adulto , Antiasmáticos/metabolismo , Anticorpos Monoclonais/metabolismo , Antígenos CD/efeitos dos fármacos , Antígenos CD20/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/metabolismo , Linfócitos B/imunologia , Complexo CD3/efeitos dos fármacos , Células Cultivadas , Técnica Direta de Fluorescência para Anticorpo , Humanos , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Ativação Linfocitária , Extratos Vegetais/uso terapêutico , Receptores de IgE/efeitos dos fármacos , Receptores de IgG/efeitos dos fármacos , Receptores de Interleucina-2/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Recently we have isolated four active components from Tanshen (the root of Salvia miltiorrhiza Bunge, Labiatae) responsible for the anti-allergic activities. In this study, the molecular mechanism of action of tanshinones for the inhibition of mast cell degranulation was investigated by testing their effects on the signaling components of the high affinity IgE receptor FcepsilonRI. Activation of FcepsilonRI produced immediate tyrosine phosphorylation of Syk, mitogen-activated protein kinase extracellular signal-regulated kinase, ERK1/ERK2 (p44, p42), and phospholipase Cgamma2 (PLCgamma2). 5,16-Dihydrotanshinone-I possessed the strongest inhibitory effects on mast cell degranulation and markedly reduced FcepsilonRI-mediated tyrosine phosphorylation of ERK and PLCgamma2. This suggests that tanshinones possibly exert their anti-allergic activities by affecting FcepsilonRI-mediated tyrosine phosphorylation of ERK and PLCgamma2. Abbreviations. FcepsilonRI:high affinity IgE receptor ERK:extracellular signal regulated kinase PLC: phospholipase C
Assuntos
Anti-Inflamatórios/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Receptores de IgE/efeitos dos fármacos , Salvia miltiorrhiza , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Degranulação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Proteínas Quinases Ativadas por Mitógeno/química , Fenantrenos/administração & dosagem , Fenantrenos/farmacologia , Fenantrenos/uso terapêutico , Fosfolipase C gama , Fosforilação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Ratos , Fosfolipases Tipo C/química , Tirosina/químicaRESUMO
Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion (IC50 value, 5 microM). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor (FcepsilonRI), such as Syk, PLCgamma1, and PLCgamma2.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells (IC50 values, 10-20 microM). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.
Assuntos
Linhagem Celular Tumoral , Dopaminérgicos/farmacologia , Mastócitos/citologia , Óxido Nítrico/biossíntese , Animais , Bromocriptina/farmacologia , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/fisiologia , Clozapina/farmacologia , Dopamina/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Precursores Enzimáticos/metabolismo , Precursores Enzimáticos/farmacologia , Haloperidol/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Lipopolissacarídeos/farmacologia , Mastócitos/fisiologia , Camundongos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Nitritos/metabolismo , Fosfolipase C gama , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/farmacologia , Quercetina/farmacologia , Receptores de IgE/efeitos dos fármacos , Transdução de Sinais/fisiologia , Quinase Syk , Tetra-Hidronaftalenos/farmacologia , Fosfolipases Tipo C/metabolismo , Fosfolipases Tipo C/farmacologia , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
High-affinity IgE receptor FcepsilonRI is key molecule in the IgE-mediated allergic reactions. Epigallocatechin-3-gallate (EGCG) has a suppressive effect of the expression of the FcepsilonRI. We show here that EGCG highly associates with plasma membrane microdomains, lipid rafts. The disruption of these lipid rafts caused a reduction of the amount of raft-associated EGCG and the FcepsilonRI -suppressive effect of EGCG. These results suggest that the interaction between EGCG and the lipid rafts is important for EGCG's ability to downregulate FcepsilonRI expression.
Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Antagonistas dos Receptores Histamínicos H1 , Microdomínios da Membrana/fisiologia , Receptores de IgE/efeitos dos fármacos , Chá , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Humanos , Microdomínios da Membrana/efeitos dos fármacosRESUMO
Mast cells express the receptor tyrosine kinase kit/stem cell factor receptor (SCFR) which is encoded by the proto-oncogene c-kit. Ligation of SCFR induces its dimerization and activation of its intrinsic tyrosine kinase activity leading to activation of Raf-1, phospholipases, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinases. However, little is known about the downstream signals initiated by SCFR ligation except for activation of extracellular signal-regulated kinases. The murine mast cell line, MC/9, synthesizes and secretes TNF-alpha following the aggregation of high affinity Fc receptors for IgE (Fc epsilonRI). Ligation of SCFR or Fc epsilonRI on MC/9 cells resulted in the activation of all three MAP kinase family members, extracellular signal-regulated kinases, c-Jun amino-terminal kinase (JNK), and p38. Stem cell factor (SCF)-induced activation of JNK and p38 was insensitive to wortmannin, cyclosporin A, and FK506 whereas activation of these kinases through Fc epsilonRI was sensitive to these drugs. Coligation of SCFR augmented Fc epsilonRI-mediated activation of MAP kinases, especially JNK activation, and SCF augmented Fc epsilonRI-mediated TNF-alpha production in MC/9 cells, although SCF alone did not induce TNF-alpha production. This augmentation by SCF was regulated at the level of transcription, at least in part, since the promoter activity of TNF-alpha was enhanced following addition of SCF. These results demonstrate that SCF can augment Fc epsilonRI-mediated JNK activation and cytokine gene transcription but via pathways that are regulated differently than the ones activated through Fc epsilonRI.
Assuntos
Adjuvantes Imunológicos/fisiologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Mastócitos/enzimologia , Proteínas Quinases Ativadas por Mitógeno , Proteínas Proto-Oncogênicas , Receptores de IgE/fisiologia , Fator de Células-Tronco/fisiologia , Fator de Necrose Tumoral alfa/biossíntese , Sequência de Aminoácidos , Androstadienos/farmacologia , Animais , Antígenos/farmacologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/efeitos dos fármacos , Linhagem Celular , Ciclosporina/farmacologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/imunologia , Regulação da Expressão Gênica/imunologia , Proteínas Quinases JNK Ativadas por Mitógeno , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno , Dados de Sequência Molecular , Ovalbumina/imunologia , Ovalbumina/farmacologia , Polienos/farmacologia , Regiões Promotoras Genéticas/imunologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptores de IgE/efeitos dos fármacos , Receptores de IgE/metabolismo , Transdução de Sinais/imunologia , Sirolimo , Fator de Células-Tronco/efeitos dos fármacos , Fator de Células-Tronco/metabolismo , Tacrolimo/farmacologia , Fator de Necrose Tumoral alfa/genética , Wortmanina , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
The efficacy of the Chinese herbal therapy (Zemaphyte) has been well established as a treatment for atopic eczema (AE) in clinical trials. The purpose of this study was to probe the immunological changes that occurred when patients were treated with the herbs for a period of 8 weeks. This treatment decreased serum IgE complexes (p less than 0.05) but did not affect total serum IgE or CD23 expression on peripheral blood monocytes. Peripheral blood mononuclear cells from patients before and after treatment were cultured overnight with interleukin 4 and the ability of this cytokine to induce CD23 on monocytes from treated patients was found to be significantly diminished (p less than 0.01). Soluble interleukin 2 receptor and soluble vascular cell adhesion molecule were both raised in the serum of AE patients compared to control individuals. Both these parameters were decreased following treatment (p less than 0.05). All these changes coincided with improvement in erythema and surface damage scores. There was no alteration in soluble intracellular adhesion molecule or soluble CD23. The results of these investigations would suggest that this herbal treatment has the ability to target various immunological parameters which may be involved in the pathogenesis of AE.
Assuntos
Dermatite Atópica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Administração Oral , Adulto , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/efeitos dos fármacos , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Eritema/tratamento farmacológico , Eritema/patologia , Feminino , Humanos , Imunoglobulina E/biossíntese , Imunoglobulina E/sangue , Imunoglobulina E/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Receptores de IgE/efeitos dos fármacos , Receptores de Interleucina-2/efeitos dos fármacos , Solubilidade , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/efeitos dos fármacosRESUMO
As previously reported, protoporphyrin plus long-wavelength UV light (PP/UVA) inhibits IgE-mediated degranulation of mouse bone marrow-derived mast cells, as assessed by measurement of the release of beta-hexosaminidase. This inhibitory effect was seen with cells sensitized with IgE either before or after PP/UVA treatment (57.8 and 55.3% inhibition, respectively). PP/UVA did not dissociate IgE already bound to cells as assessed either by measuring release of bound 125I-IgE or by flow cytometric analysis. Results from immunoadsorption followed by SDS-PAGE analysis suggested that PP/UVA treatment may cause stable conjugation of IgE to its receptor. In unsensitized cells, PP/UVA did not cause conjugation of the unoccupied Fc epsilon RI to other proteins in the plasma membrane. Nevertheless, Scatchard analysis revealed that PP/UVA decreased the number of Fc epsilon RI per cell by 37% (0.95 x 10(5) vs 1.51 x 10(5)/cell), whereas affinity of the receptor for IgE was comparable between PP/UVA-treated and untreated cells (3.40 nM vs 3.27 nM). Flow cytometric analysis also confirmed the decrease in Fc epsilon RI number in PP/UVA-treated unsensitized mouse bone marrow-derived mast cells. Although 84% of PP/UVA-treated and 82% of untreated cells expressed positive fluorescence when stained with FITC-conjugated IgE, fluorescence intensity was reduced by 40% after PP/UVA treatment. We conclude that PP/UVA alters the conformational structure and/or number of Fc epsilon RI expressed on the mast cell surface. This effect could potentially explain the ability of PP/UVA to inhibit mast cell secretory function and may be related to an ability of PP/UVA to alter the properties of the plasma membrane.
Assuntos
Mastócitos/efeitos dos fármacos , Terapia PUVA , Receptores de IgE/efeitos dos fármacos , Animais , Células da Medula Óssea , Degranulação Celular/efeitos dos fármacos , Células Cultivadas , Imunoglobulina E/metabolismo , Mastócitos/fisiologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
A remarkable "steroid sparing" effect of Saiboku-to was noted within 6 to 12 months of treatment in steroid-dependent asthmatic patients. Saiboku-to spared the downregulation of glucocorticoid receptor of human lymphocytes, plasma ACTH, and cortisol levels. It also spared downregulation of beta 2 receptor by beta 2 agonists and suppressed mACh receptor at the same time. Saiboku-to increased tyrosine aminotransferase (TAT) production, which was inhibited by actinomycin-D, thus having steroid-like activity. In mite-allergic asthma, Saiboku-to inhibited the induction of expression of IgE-Fc epsilon R/CD23 in the lymphocytes by mite allergen. It also inhibited IgE production by mite allergens. In experimental asthma in guinea pigs the use of Saiboku-to resulted in a decrease in the number of eosinophils in the bronchoalveolar lavage fluid during late asthmatic response. These findings suggest that Saiboku-to may be effective in inhibiting both the expression of IgE-Fc epsilon R2 and the induction of expression of IgE-Fc epsilon R1. Saiboku-to also has a steroid-like action and polyhedral anti-asthmatic activities.