Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.65 (Der p 1)
 346 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased attention has recently been directed at the possibility that the clinical efficacy of immunotherapy might be elaborated by alteration of T-cell reactivity. However, there is no general agreement among different investigators regarding the effect of immunotherapy on Th-cell reactivity. Peripheral blood mononuclear cells (PBMCs) from 15 nonatopic subjects and 76 patients with perennial allergic rhinitis (18 untreated patients and 58 patients on immunotherapy) were cultured in the absence and in the presence of a major Dermatophagoides farinae allergen, Der f 1, and the levels of IgE, interleukin-5 (IL-5), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatants were determined. The difference between the absence and presence of Der f 1 was calculated to consider the Der f 1-dependent synthesis of IgE, IL-5, IFN-gamma and TNF-alpha. The levels of Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha were significantly higher in the untreated group than in the nonatopic group, whereas Der f 1-dependent synthesis of IFN-gamma was significantly lower in the untreated group than in the nonatopic group. Immunotherapy decreased the enhanced Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha, and further decreased the suppressed Der f 1-dependent synthesis of IFN-gamma as the therapy proceeded. The levels of Der f 1-dependent synthesis of IgE and IL-5 did not differ between nonatopic individuals and patients whose duration of immunotherapy was 10 or more years. The levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, were correlated significantly with the levels of symptom scores. In addition, the levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, differed significantly between good and poor responders. In conclusion, immunotherapy for perennial allergic rhinitis may possibly work via induction of tolerance or anergy of both Th1- and Th2 cells. However, our study is likely to support a view that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the tolerance of Th2- rather than Th1 cells. In addition, suppression of IgE synthesis is also likely to be linked to the clinical efficacy of immunotherapy for perennial allergic rhinitis.
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PMID:Immunotherapy suppresses both Th1 and Th2 responses by allergen stimulation, but suppression of the Th2 response is a more important mechanism related to the clinical efficacy of immunotherapy for perennial allergic rhinitis. 971 13

The herbal medicine shoseiryu-to is an effective agent in the treatment of allergic rhinitis. However, the mechanism by which it exerts its action in improving patient symptoms remains unclear. It might affect the allergen-induced TH1 and/or TH2 responses. This study investigated whether the herbal medicine could affect cytokine synthesis by peripheral blood mononuclear cells (PBMCs) in response to the major Dermatophagoides farinae (D. farinae) allergen, Der f 1. PBMCs were obtained from 15 patients with perennial allergic rhinitis due to D. farinae, and were stimulated for 96 h with 10 micrograms/ml Der f 1 in the presence or absence of 45 mg/ml shoseiryu-to. The culture supernatants were harvested to determine the synthesis of IgE, interleukin 5 (IL-5), IL-6, IL-10, interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha). The agent did not affect the allergen-induced synthesis of IL-5, IL-6 and IFN-gamma, but somewhat decreased the synthesis of IgE and IL-10. This study highlighted an interesting pharmacological action of shoseiryu-to to substantially inhibit the allergen-induced synthesis of TNF-alpha. Our study suggests that the shoseiryu-to may alleviate nasal symptoms in allergic rhinitis through control of the allergen-induced inflammatory process.
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PMID:The herbal medicine shoseiryu-to inhibits allergen-induced synthesis of tumour necrosis factor alpha by peripheral blood mononuclear cells in patients with perennial allergic rhinitis. 987 11

The polarization of the immune response toward a Th2 or a Th1 profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such as CD80 and CD86 expressed by DCs, the polarizing cytokine environment during DC--T-cell interaction, and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides pteronyssinus, on these different parameters was evaluated comparatively on monocyte-derived DCs obtained from healthy donors, from pollen-sensitive patients, or from patients sensitive to Dermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite--sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the production of proinflammatory cytokines, tumor necrosis factor--alpha and interleukin (IL)-1 beta, and the type 2 cytokine IL-10. No changes in the release of IL-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite-sensitive patients stimulated by autologous Der p 1--pulsed DCs preferentially produced IL-4 rather than interferon-gamma. These effects were abolished in the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs from house dust mite--sensitive patients, in contrast to DCs from healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated with the allergic reaction developed in response to house dust mite exposure. (Blood. 2001;98:1135-1141)
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PMID:Th2 polarization by Der p 1--pulsed monocyte-derived dendritic cells is due to the allergic status of the donors. 1149 62

A whole blood culture technique was used to establish conditions for stimulating the production of cytokines by cord blood lymphocytes. The cultures were stimulated with mitogens (concanavalin A and phytohaemagglutinin) and allergens (beta-lactoglobulin (BLG), ovalbumin (OVA) and house dust mite (Der p 1)) at a range of concentrations. Interleukin (IL-) 2, IL-4, IL-10, IL-13 and interferon-gamma (IFN-gamma) concentrations were assayed in the supernatants at 24, 48 and 72 h. Stimulation with mitogens but not allergens induced increases in IL-2 and IL-13 concentrations. IFN-gamma was strongly induced by mitogenic stimulation: maximal responses were seen at 48 h. Stimulation with the allergens also induced an increase in IFN-gamma concentration which was maximal for 100 microg/ml of BLG and OVA. Der p 1 induced the highest IFN-gamma production among the allergens. IL-4 concentrations were increased in mitogen and Der p 1 stimulated cultures. This was maximal at 48 and 24 h, respectively. IL-10 was induced with mitogen and allergen stimulation. Thus, this study has established conditions for assessing production of lymphocyte-derived cytokines in a simple whole umbilical cord blood culture system.
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PMID:Production of lymphocyte-derived cytokines by whole umbilical cord blood cultures stimulated with mitogens and allergens. 1267 Apr 46

This study investigated the influence of prenatal exposure to house dust mite (HDM, D. pteronyssinus) on interleukin (IL)-2, interferon-gamma (IFN-gamma) and IL-4 producing CD4(+) and CD8(+) T lymphocytes in cord blood as well as on the development of sensitization and occurrence of atopic dermatitis (AD) as the first symptom of allergy during the first year of life. Dust samples (n = 22) were collected by vacuum cleaning the maternal mattress during early to mid-pregnancy. In these samples, the amount of the major HDM antigen (Der p 1) was assessed by a sensitive enzyme-linked immunosorbent assay technique (detection limit 0.004 microg/g dust). Flow cytometry was used to determine cord blood lymphocyte subtypes and to quantify the intracellular amounts of IL-2, IFN-gamma and IL-4 produced by cord blood CD4(+) helper and CD8(+) cytotoxic T lymphocytes, both spontaneously and after stimulation with phorbol-12-mirystate-13-acetate and ionomycin. Children were followed for 1 yr for the presence of symptoms associated with allergy. In addition, at the age of 1 yr specific IgE to different classical inhalant and food allergens was measured. Higher prenatal exposure to Der p 1 (>0.2 microg/g dust) was associated with a significant lower percentage of IFN-gamma producing stimulated CD4(+) T lymphocytes, compared with lower prenatal Der p 1 exposure (p = 0.03). The presence of AD during the first year of life (n = 9) was associated with an increased number of naive CD4(+) CD45RA(+) lymphocytes (p = 0.03), with an increased spontaneous IL-4 production by CD8(+) lymphocytes (p = 0.04) and with a decreased percentage of IFN-gamma producing stimulated CD4(+) lymphocytes (p = 0.04). Furthermore, exposure to HDM during pregnancy tended to be higher in mothers of children with AD during the first year of life when compared with those without AD (p = 0.08). This study shows that the level of prenatal exposure to Der p 1 influences the immune profile of cord blood T lymphocytes and the clinical outcome in early life. Therefore, the prenatal environment must be regarded as a possible early risk factors for allergic diseases in children.
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PMID:Prenatal exposure to house dust mite allergen (Der p 1), cord blood T cell phenotype and cytokine production and atopic dermatitis during the first year of life. 1530 39

The apparent complexity of allergen-specific T-cell response in terms of epitope usage in humans is a potential barrier to peptide-based immunotherapy for allergy. A knowledge of cross-reacting T-cell epitopes of common allergens might have an impact on the development of vaccines for immunotherapy. We examined the efficiency of vaccinating with plasmid DNA coding only human T-cell epitopes on the suppression of allergic reactions in mice. BALB/c mice that received an injection of mixed naked DNA plasmids encoding the five classes of human T-cell epitopes on Der p 1 and Der p 2 produced a significant reduction in total and Der p-specific immunoglobulin E (IgE) synthesis. In Der p specific-IgG2a antibody responses, vaccinated mice showed more prominent responses than controls. Higher levels of interferon-gamma, a Th1 cytokine associated with the suppression of IgE production, were found in the sera of vaccinated mice. Histologic studies showed a marked reduction in the infiltration of inflammatory cells in the lung tissues of vaccinated mice vs. controls. These results suggest that vaccination with DNA encoding human T-cell epitopes effectively inhibits allergic responses in mice and might induce cross-regulation on helper T-cell level in vivo.
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PMID:Vaccination with DNA encoding human T-cell epitopes suppresses Der p induced allergic responses in mice. 1587 44