Search

Background: Mast cells play an important role in allergic reactions by releasing potent mediators, including histamine and platelet-activating factor (PAF), upon activation. We recently reported that a biotinylated heptapeptide (peptide 2), D-Lys(Biotinyl)-Trp-Tyr-Lys-Asp-Gly-Asp, which is highly stable in the plasma, inhibits PAF bioactivity and anaphylactic hypothermia in vivo. However, the effects of this peptide on allergy induction by mast cells have not been investigated. Methods and Results: Several biotinylated heptapeptides, including peptide 2, inhibited IgE/antigen-stimulated degranulation in RBL-2H3 cells. Peptide 2 also markedly inhibited the degranulation induced by calcium ionophore A23187. All peptides (peptide 1, 2 and 3) inhibited activating stimuli-induced increase in intracellular Ca2+ levels. The transforming growth factor-alpha shedding assay indicated that peptide 2 antagonized against the histamine H1 receptor. Furthermore, peptide 2 inhibited histamine-induced rat paw edema. Conclusion: These results highlight the potential of peptide 2 in the prevention and treatment of various allergic diseases mediated by mast cell activation. [ABSTRACT FROM AUTHOR]

Background: Mast cells play an important role in allergic reactions by releasing potent mediators, including histamine and platelet-activating factor (PAF), upon activation. We recently reported that a biotinylated heptapeptide (peptide 2), D-Lys(Biotinyl)-Trp-Tyr-Lys-Asp-Gly-Asp, which is highly stable in the plasma, inhibits PAF bioactivity and anaphylactic hypothermia in vivo. However, the effects of this peptide on allergy induction by mast cells have not been investigated. Methods and Results: Several biotinylated heptapeptides, including peptide 2, inhibited IgE/antigen-stimulated degranulation in RBL-2H3 cells. Peptide 2 also markedly inhibited the degranulation induced by calcium ionophore A23187. All peptides (peptide 1, 2 and 3) inhibited activating stimuli-induced increase in intracellular Ca2+ levels. The transforming growth factor-alpha shedding assay indicated that peptide 2 antagonized against the histamine H1 receptor. Furthermore, peptide 2 inhibited histamine-induced rat paw edema. Conclusion: These results highlight the potential of peptide 2 in the prevention and treatment of various allergic diseases mediated by mast cell activation. [ABSTRACT FROM AUTHOR]

The article presents a study focusing on suppression of Th2 cytokines and Trans-acting T-cell-specific transcription factor GATA-3 in EL-4 T cells by cyanidin-3-glucoside. The findings of the study include cyanidin-3-glucoside chloride (C3G) produced in activated EL-4 T cells but not Thl cytokines, inhibition of IL-13 promoter reporter plasmids, and conclusion that C3G may has potential as an anti-allergic agent.

Magnolia species have been used for the treatment of allergic diseases in Asia as folk medicine; however, the cellular and molecular mechanisms of its anti-allergic effects have rarely been investigated. In this study, we demonstrated that a methanolic extract of the fructus of Magnolia denudata has suppressive effects on Th2 cytokine production such as IL-4 and IL-13, but not IFN-γ and IL-17, produced by both phorbol 12-myristate 13-acetate/ionomycin (PI)- and CD3/CD28-stimulated EL-4 T cells. Moreover, the mRNA expression of Th2 cytokines was significantly inhibited, and luciferase activity in cells transiently transfected with IL-4 or IL-13 promoter reporter plasmids was suppressed by M. denudata, indicating that M. denudata may regulate these expression at the transcriptional level. Western blot analysis for transcription factors involved in the cytokine gene expression indicated that the activation of c-Jun was significantly downregulated in the nucleus of cells, while the activations of nuclear factor of activated T cells, nuclear factor kappa B and c-Fos, were not affected. Furthermore, the mRNA expression and nuclear translocation of GATA-binding protein 3, a key transcriptional factor for Th2 commitment and Th2 cytokine expression, but not T-bet and RORγt, were dramatically downregulated by M. denudata. Treatment with M. denudata suppressed the phosphorylation of p38 mitogen-activated protein kinase; however, the PI-induced phosphorylation of extracellular signal-related kinase and c-Jun N-terminal kinase was unaffected. Taken together, our study indicated that M. denudata inhibited IL-4 and IL-13 expression, possibly through regulation of p38 mitogen-activated protein kinase phosphorylation and selective transcription factors, such as GATA-3 and c-Jun, in EL-4 T cells. [ABSTRACT FROM AUTHOR]

The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 mug/ml haemocyanin and various concentrations of the agents. Low concentrations (<1.5 × 10[sup -4] M) of EP and DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 × 10[sup -4] M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 × 10[sup -4] M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 × 10[sup -4] M of the agents and the expression of molecules were examined by flow cytometer 24 h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro. [ABSTRACT FROM AUTHOR]

The influence of an anti-allergic agent, suplatast tosilate (IPD-1151T; (±)-[2-[4-(3-ethoxy-2-hydroxypropoxy)phenyl-carbamoyl]-ethyl] dimethylsulfonium p-toluenesulfonate) on allergic bronchoconstriction induced by allergen and methacholine (MCh) were examined in mice. BALB/c mice were sensitized by intraperitoneal injection of dinitrophenylated-keyhole limpet hemocyanin (DNP-KLH) mixed with Al(OH)[sub 3] (DNP-KLH). IPD-1151T was administered orally once a day for either 5 or 14 days in doses of 10, 30 or 100 mg/kg. Bronchoconstriction was measured 24 h after the final drug administration. IPD-1151T inhibited both antigen- and MCh-mediated bronchoconstriction in actively sensitized mice. The inhibition induced was closely related to the dose and frequency of oral administration of the agent. We also examined the effect of IPD-1151T on IgE production in response to DNP-KLH immunization. IPD-1151T inhibited dose-dependently both total and specific IgE concentrations in serum prepared from mice 15 days after im munization. These results strongly indicate that IPD-1151T inhibits IgE production in vivo and results in attenuating effect on bronchoconstriction. [ABSTRACT FROM AUTHOR]

β-adrenoceptor stimulants exhibit both bronchodilating and anti-allergic activities. KWD 2131 is a new β-agonist with preferably anti allergic property. In an earlier study, nebulized KWD 2131 in a non-bronchodilating dose (0.25 - 0.50 mg) did not give significant protection against immediate reaction. The present study evaluated whether an increased nebulized dose of the new compound (5 mg) could protect against either immediate and/or late responses. The response was compared with a nebulized dose of terbutaline (5 mg) and with twice the recommended dose DSCG (40 mg). The study included 10 patients with known allergic asthma. It was designed as a single-blind cross-over trial with randomized allocation of the drugs. Lung functions were measured spirometrically and by body-plethysmograph; flow volume curves were drawn. KWD 2131 gave no significant protection against immediate reaction. Both terbutaline and DSCG did so, terbutaline being more efficient. Contrary to the β-agonists, DSCG also gave protection against late response. [ABSTRACT FROM AUTHOR]

The selective anti-allergic effect of a new β-agonist, KWD 2131, in inhibiting allergen-provoked asthma was compared with that of placebo in a double-blind crossover study. Non-bronchodilating doses were given by inhalation to 12 asymptomatic patients with extrinsic asthma. KWD 2131 showed a marginal anti-allergic effect. A significantly better effect than that with placebo was obtained at only one time of measurement after challenge (P <0.05). The reproducibility of the allergen challenge was also evaluated. The mean maximum decrease in FEV1 during three different allergen-challenge procedures was 37, 31, and 38%, respectively. The difference was not statistically significant. [ABSTRACT FROM AUTHOR]

Degranulation of IgE-sensitized rat mast cells by antigen was studied quantitatively in vitro and in vivo by electron microscopy. The inhibition of this degranulation by an anti-allergic drug, N-(3,4-dimethoxycinnamoyl)anthranilic acid (Tranilast), was also examined both in vitro and in vivo. In the in vitro study using peritoneal mast cells, alteration of the granules, cavity formation by fusion of the perigranular membrane and granule discharge due to fusion of the cavity membrane with the cell membrane were observed and were accompanied by histamine release. Scanning electron microscopy disclosed the extrusion of smooth, round bodies from pores formed on the cell surface. In the in vivo study of passive cutaneous anaphylaxis (PCA), the characteristic features of mast cell degranulation were obvious 5 min after the injection of antigen; leakage of dye increased progressively from 5 to 30 min but was not found at 6 h. From quantitative analysis of the substructure of mast cells, it was demonstrated that degranulation of IgE-sensitized mast cells induced by antigen was achieved by sequential exocytosis both in vitro and in vivo. Tranilast inhibited these changes to a remarkable extent and it was concluded that the inhibition of mast cell degranulation by this drug might play an important role in anti-allergic treatment. [ABSTRACT FROM AUTHOR]

Background Eosinophil cationic protein (ECP) is a highly basic protein (p1 over ii) with molecular weight ranging from 18.5 to 22 kDa, and is released upon eosinophil activation. ECP is stored in the cosinophil granules and has potent bactericidal, helminthotoxic, cytotoxic and neurotoxic effects. ECP levels in serum and other body fluids are often elevated in allergic diseases and other inflammatory conditions and their measurement may give information regarding eosinophil involvement in a pathological process. Material and Methods We evaluated the serum levels of eosinophil cationic protein (ECP), assayed using an ECP radioimmunoassay kit, and the effect of an anti-allergic agent, ketotifen, which has a potent anti-eosinophil activity, in atopic dermatitis (AD) patients. Serum ECP levels in AD patients correlated with the severity of AD as determined in clinical evaluations. Results In patients with severe and moderate AD, serum ECP levels were significantly higher (31.04 ± 3.35 &mue;g/I, n = 32) than in non-atopic controls (4.92 ± 1.06 &mue;g/I, a = 16) (P < OA)O1). However, no significant correlation was observed between serum ECP and IgE levels, or between serum ECP levels and peripheral eosinophil count. After a 4-week administration of ketotifen (1 mg; twice a day), in AD patients with serum ECP levels more than 20 &mue;g/I (n 14), serum ECP levels decreased significantly (from 44.17 ± 4.53 to 18.46 ± 3.35 &mue;g/I, P

We evaluated the serum levels of major basic protein (MBP), assayed using an MBP radioimmunoassay kit, and the effect of an anti-allergic agent, ketotifen, which has strong anti-eosinophil activity, in 56 atopic dermatitis (AD) patients. The serum MBP level was significantly lower (660.11 ± 34.52 ng/ml, P < 0.05) after administration of ketotifen (1 mg twice a day) for 8 weeks than before treatment (774.98 ± 48.64 ng/ml). These findings suggest that serum MBP levels are a useful indicator of AD activity and that anti-allergic agents can have an effect on eosinophil involvement in AD. [ABSTRACT FROM AUTHOR]