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)

A disintegrin and metalloprotease (ADAM) proteins have wide ranging functions, including proteolytic cleavage of cell surface molecules, cell fusion, cell adhesion and intracellular signalling. Recent evidence suggests the involvement of ADAM8 in allergic responses. For instance, ADAM8 is amongst a number of genes up-regulated in experimentally induced asthma in animals. In order to further define the involvement of ADAM8 in allergic responses, we sought in the first instance to examine its distribution on human peripheral blood B cells, resting and activated T cells, monocyte subsets and monocyte derived dendritic cells. Here we demonstrate for the first time ADAM8 protein expression on B cells and dendritic cells, and its higher expression on CD14(2+)CD16(-) monocytes compared to CD14(+)CD16(+) cells. Immature dendritic cells expressed low levels of ADAM8 when treated with a combination of GM-CSF and IL-4, but stimulation with LPS resulted in a higher level of expression, which was TLR-4 independent. Up-regulation of ADAM8 expression on dendritic cells was also observed after stimulation with TNF-alpha, but not after stimulation with anti-CD40. The demonstration of ADAM8 expression on these cells provides an opportunity for addressing the potential role of inhaled protease allergens, such as Der p 1, in modulating ADAM8 functions, particularly with regards to innate immune responses by dendritic cells and IgE synthesis by B cells.
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PMID:The detection of ADAM8 protein on cells of the human immune system and the demonstration of its expression on peripheral blood B cells, dendritic cells and monocyte subsets. 1727 Jul 7

Immune reactivity is a key issue in the evaluation of the quality of recombinant allergens as potential reference materials. Within the frame of the CREATE project, the immune reactivity of the natural and recombinant versions of the major allergens of birch pollen (Bet v 1), grass pollen (Phl p 1 and 5), olive pollen (Ole e 1), and house dust mite (Der p 1 and 2, and Der f 1 and 2) was analysed. The IgE binding capacity of the allergens was studied by direct RAST and RAST inhibition, and their biological activity by basophil histamine release, using sera of allergic patients selected across Europe. For birch pollen, rBet v 1 is an excellent mimic of the natural allergen. For grass pollen, rPhl p 1 showed a significant lower IgE reactivity and was not considered a suitable candidate, whereas rPhl p 5a exhibited an immune reactivity closer to that of its natural counterpart. For olive, rOle e 1 had a lower IgE binding capacity in RAST but a higher biological activity in histamine release. For house dust mite, recombinant group 1 allergens were significantly less potent than their natural counterparts, but recombinant group 2 allergens were close mimics of their natural homologues.
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PMID:Immune reactivity of candidate reference materials. 1739 27

Several cysteine and serine protease allergens have been cloned from house dust mites, including Der p 1, Der p 3, Der p 6, and Der p 9. A significant body of evidence suggests that these allergens mimic helper T (Th) 2 cell adjuvants. Der p 1 cleaves CD23 from activated B cells and CD25 from T cells. Der p 1 proteolytically degrades tight junctions in lung epithelium and causes release of proinflammatory cytokines from bronchial epithelial cells, mast cells, and basophils. These synergistic effects of mite enzyme allergens may promote IgE synthesis and have direct inflammatory effects on lung epithelium, which could explain why mite allergens are associated with asthma. The crystal structures of the proenzyme and mature forms of Der p 1 have been determined, as have the structures of other indoor allergens that are not enzymes (eg, Der p 2, Fel d 1, and Bla g 2). Cockroach allergens are strongly associated with asthma in US inner cities, yet none of the cockroach allergens that have been cloned are proteolytic enzymes. Thus although mite proteases allergens may act as Th2 adjuvants, a paradoxical effect is that other allergens may elicit strong Th2 responses in the absence of enzyme activity.
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PMID:Proteases as Th2 adjuvants. 1769 45

Inherited atopic diseases of humans arise from adverse adaptive humoral responses to noninfectious environmental allergens. We previously reported that allergen-specific IgG1 provides more reliable heritability estimates for responses to allergens than total IgE. Genome scans were done for 91 Caucasian nuclear families with history of atopy for total IgE and IgG1 produced against a common major allergen from house dust mite, Der p 1. Suggestive associations for Der p 1-IgG1 production were found at 7 quantitative trait loci (QTL) (logarithm of the odds, LOD > or = 1.23; p < or = 0.009) with QTL-specific heritabilities of 73%-80%. Scans using total IgE found suggestive associations for 12 QTLs (LOD > or = 1.44; p < or = 0.004), but QTL-specific heritabilities only in the range of 30%-35%. Allergen-specific IgG1 is a suitable "endophenotype" to be used in searches for genes associated with atopy-associated humoral immune responses to common aeroallergens.
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PMID:Search for quantitative trait loci of atopy-associated immune responses using allergen-specific IgG1 as an "endophenotype". 1796 72

House dust mite allergy occurs in 10-20% of the population. Improvement of the present immunotherapy requires detailed knowledge about the structure of the allergens. Mimotopes selected from phage peptide libraries imitate the conformational epitopes of a natural allergen. The aim of our study was to generate epitope mimics for the two major allergens of house dust mite. When the monoclonal anti-Der p 1 and anti-Der p 2 antibodies were used for biopannings, mimotopes were selected which bound also specific IgE from human allergic patients' sera. The conformational matching of these mimotopes on the 3D structure of the natural allergens determined discontinuous epitopes in both cases, representing conformational B-cell epitopes relevant for binding of human IgE. Therefore, these mimotopes are potential candidates for the directed induction of blocking antibodies and epitope-specific immunotherapy of mite allergy.
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PMID:Mimotopes identify conformational B-cell epitopes on the two major house dust mite allergens Der p 1 and Der p 2. 1796 53

As an alternative approach to conventional allergen-specific immunotherapy, transgenic rice seed expressing a major house dust mite (HDM) allergen, Der p 1, was developed as an edible vaccine. The C-terminal KDEL-tagged Der p 1 allergen specifically accumulated in seed endosperm tissue under the control of the endosperm-specific GluB1 promoter. Der p 1 reached a maximum concentration of 58 microg/grain and was deposited in the endoplasmic reticulum (ER)-derived protein body I (PB-I). Plant-derived Der p 1 was posttranslationally modified with high-mannose-type glycan structures. Glycosylated Der p 1 displayed reduced IgE binding capacity in comparison with its unglycosylated counterpart in vitro. Our results indicate that transgenic Der p 1 rice seeds are a safe, potential oral delivery vaccine for the treatment of HDM allergy.
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PMID:Generation of a transgenic rice seed-based edible vaccine against house dust mite allergy. 1798 39

Mite allergen exposure can lead to sensitization in genetically predisposed individuals, and the development of asthma in previously sensitized individuals. The major allergens of mites belong to Dermatophagoides spp. and Blomia tropicalis (Bt). Various allergens of Bt have been cloned and sequenced. Some of them show homology sequence with purified allergens from Dermatophagoides pteronissynus (Dp). Recently, the allergen group 1 from Bt, Blo t 1, was cloned and sequenced at our laboratory. Recombinant Blo t 1 showed 35 % of identity and 50% of similarity with group 1 allergens as Der p 1 (from Dp), Der f 1 (from D. farinae) and Eur m 1 (from Euroglyphus maynei) at amino acid level. This would suggest that cross-reactivity between allergens of different mite species could exist. Here, we analyzed the crossreactivity between group 1 allergens from mites using recombinant proteins and monoclonal antibodies against them. ELISA inhibition assay showed that crossreactivity between homologous allergens from Dermatophagoides spp. is high, but it is low to moderate between mites from different species. IgE-reactivity analysis using serum samples from allergic individuals revealed a strong reactivity of rBlo t 1 for serum samples from subjects with highly positive reaction to Bt extract in skin test, but lack of reactivity of this protein with serum samples from individuals with highly positive reaction to house dust mite extract in the skin test. These results suggest that it is important to include Bt allergens in routine skin test in order to improve the diagnostic accuracy and precision of allergies.
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PMID:Analysis of cross-reactivity between group 1 allergens from mites. 1861 45

The group 1 mite allergens Der f 1 and Der p 1 are potent allergens excreted by Dermatophagoides farinae and Dermatophagoides pteronyssinus, respectively. The human immunoglobulin E antibody responses to the group 1 allergens show more cross-reactivity than the murine immunoglobulin G antibody responses, which are largely species specific. Here, we report the crystal structure of the mature form of Der f 1, which was isolated from its natural source, and a new high-resolution structure of mature recombinant Der p 1. Unlike Der p 1, Der f 1 is monomeric both in the crystalline state and in solution. Moreover, no metal binding is observed in the structure of Der f 1 despite the fact that all amino acids involved in Ca(2+) binding in Der p 1 are completely conserved in Der f 1. Although Der p 1 and Der f 1 share an extensive sequence identity, comparison of the crystal structures of both allergens revealed structural features that could explain the differences in murine IgG and human IgE antibody responses to these allergens. There are structural differences between Der f 1 and Der p 1 that are unevenly distributed on the allergens' surfaces. This uneven spatial arrangement of conserved versus altered residues could explain both the specificity and cross-reactivity of antibodies against Der f 1 and Der p 1.
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PMID:Crystal structures of mite allergens Der f 1 and Der p 1 reveal differences in surface-exposed residues that may influence antibody binding. 1913 6

House dust mite (HDM) allergens are the most common allergens involved in the induction of IgE-mediated hypersensitivity. Recently, epicutaneous sensitization with HDM allergens has been emphasized in the development of atopic dermatitis (AD); however, direct stimulation of canine keratinocytes by mite allergens has not been well investigated. In the present study, we investigated the effects of Der f 1, a major allergen of Dermatophagoides farinae, on cytokine and chemokine gene expression in a canine keratinocyte cell line, CPEK. CPEK constitutively expressed mRNA for TNF-alpha, IL-12p35, IL-18, GM-CSF, TGF-beta, IL-8/CXCL8, TARC/CCL17, CTACK/CCL27 and MEC/CCL28. Of all the cytokines and chemokines investigated in CPEK, transcription levels of GM-CSF, IL-8/CXCL8 and TNF-alpha mRNA were significantly enhanced by stimulation with Der f 1. The present results suggest that Der f 1 can directly augment inflammatory cytokine and chemokine production from keratinocytes, and may initiate allergic inflammation independently of Type-I hypersensitivity.
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PMID:House dust mite major allergen Der f 1 enhances proinflammatory cytokine and chemokine gene expression in a cell line of canine epidermal keratinocytes. 1944 88

Corpus Christi, TX, is a Gulf Coast city with high humidity levels year-round. There is little available data on mite species in mattress dust, allergen levels, and sensitization to different mite species in allergic patients. This study was designed to determine skin sensitization and specific serum IgE to Dermatophagoides spp. and Blomia tropicalis in patients attending an allergy clinic and to explore the mite fauna and allergen content of their mattresses. Skin-prick tests to Dermatophagoides spp. and B. tropicalis along with mite-specific IgE in the serum by enzyme-linked immunosorbent assay (ELISA) and ImmunoCAP tests were performed in allergic patients attending an outpatient allergy clinic in Corpus Christi, TX. Mite species and allergen levels were determined in mattress dust. Forty-five consecutive patients were evaluated; 10 patients had positive skin tests to Dermatophagoides pteronyssinus and B. tropicalis, 32 patients reacted only to D. pteronyssinus, and 3 patients reacted exclusively to B. tropicalis. Increased titers of D. pteronyssinus- and D. farinae-specific IgE were present and B. tropicalis-specific IgE titers were lower. Significant amounts of mites were observed in 79.5% of dust samples, with a predominance of D. pteronyssinus and D. farinae. Other mite species, such as B. tropicalis, Euroglyphus maynei, Tarsonemus spp., Tyrophagus putrescientiae, Cheyletus spp., and Oribatidae were also observed. Greater levels of Der p and Der f 1 than of Blo t 5 were present in the mattresses. D. pteronyssinus and D. farinae are the prevalent mite species in houses of allergic patients from Corpus Christi, TX. Other mite species are also found.
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PMID:Allergic sensitization to domestic mites in Corpus Christi, Texas. 1946 6


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