Base de dados : MEDLINE Pesquisa : D12.776.124.486.485.114.619.312.500 [Categoria DeCS] Referências encontradas : 216 [refinar] Mostrando: 1 .. 10   no formato [Detalhado]

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[PMID]: 28350867 [Au] Autor: Alcantara-Neves NM; Veiga RV; Ponte JC; da Cunha SS; Simões SM; Cruz ÁA; Yazdanbakhsh M; Matos SM; Silva TM; Figueiredo CA; Pontes-de-Carvalho LC; Rodrigues LC; Fiaccone RL; Cooper PJ; Barreto ML [Ad] Endereço: Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil. [Ti] Título: Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children. [So] Source: PLoS One;12(3):e0174089, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. METHODS: Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. RESULTS: Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. CONCLUSIONS: A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis". [Mh] Termos MeSH primário: Alérgenos/imunologia Hipersensibilidade/imunologia Imunoglobulina E/imunologia Testes Cutâneos/métodos [Mh] Termos MeSH secundário: Animais Ascaris lumbricoides/imunologia Brasil Gatos Criança Pré-Escolar Ensaio de Imunoadsorção Enzimática Fezes/microbiologia Fezes/parasitologia Fezes/virologia Seres Humanos Hipersensibilidade/sangue Hipersensibilidade/diagnóstico Imunoglobulina E/sangue Imunoglobulina G/sangue Imunoglobulina G/imunologia Cadeias épsilon de Imunoglobulina/genética Cadeias épsilon de Imunoglobulina/imunologia Polimorfismo de Nucleotídeo Único/imunologia Receptores de IgE/genética Receptores de IgE/imunologia Roedores Simplexvirus/imunologia Trichuris/imunologia Saúde da População Urbana/estatística & dados numéricos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Allergens); 0 (FCER1A protein, human); 0 (Immunoglobulin G); 0 (Immunoglobulin epsilon-Chains); 0 (Receptors, IgE); 37341-29-0 (Immunoglobulin E) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170828 [Lr] Data última revisão: 170828 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170329 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0174089

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[PMID]: 25952120 [Au] Autor: Fu X; Wang X; Duan Z; Zhang C; Fu X; Yang J; Liu X; He J [Ad] Endereço: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. [Ti] Título: Histone H3k9 and H3k27 Acetylation Regulates IL-4/STAT6-Mediated Igε Transcription in B Lymphocytes. [So] Source: Anat Rec (Hoboken);298(8):1431-9, 2015 Aug. [Is] ISSN: 1932-8494 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Igε via chromatin remodeling involved in B lymphocytes development. STAT6 acts as a molecular switch to regulate the higher-order chromatin remodeling via dynamically orchestrating co-activators (CBP/Tudor-SN) and co-repressors (HDAC1/PSF). Here, we demonstrated that STAT6/Tudor-SN/PSF form a complex, balancing the acetylation and deacetylation states to co-regulate IL-4/STAT6 gene transcription. In addition, we confirmed that IL-4 treatment increased the HATs activity in Ramos cells. As "active" markers, the expression of H3K9ac and H3K27ac increased after treatment with IL-4. However, transcriptional repressors such as H3K9me3 and H3K27me3 decreased in response to IL-4 stimulation. Moreover, IL-4 treatment enhanced H3 acetylation at the Igε promoter regions. Our results revealed that the Igε gene transcription is regulated by histone modifications in the IL-4/STAT6 pathway. The study will provide novel insights into the pathogenesis of allergic diseases. [Mh] Termos MeSH primário: Linfócitos B/efeitos dos fármacos Montagem e Desmontagem da Cromatina/efeitos dos fármacos Histonas/efeitos dos fármacos Cadeias épsilon de Imunoglobulina/metabolismo Interleucina-4/farmacologia Processamento de Proteína Pós-Traducional/efeitos dos fármacos Fator de Transcrição STAT6/metabolismo Transcrição Genética/efeitos dos fármacos [Mh] Termos MeSH secundário: Acetilação Animais Asma/genética Asma/imunologia Asma/metabolismo Linfócitos B/metabolismo Linhagem Celular Tumoral Modelos Animais de Doenças Regulação da Expressão Gênica Histonas/metabolismo Seres Humanos Cadeias épsilon de Imunoglobulina/genética Histona Desmetilases com o Domínio Jumonji/metabolismo Pulmão/imunologia Pulmão/metabolismo Camundongos Proteínas Nucleares/metabolismo Ovalbumina Fator de Processamento Associado a PTB Proteínas de Ligação a RNA/metabolismo Transdução de Sinais/efeitos dos fármacos Fatores de Tempo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Histones); 0 (IL4 protein, human); 0 (Immunoglobulin epsilon-Chains); 0 (Nuclear Proteins); 0 (PTB-Associated Splicing Factor); 0 (RNA-Binding Proteins); 0 (SND1 protein, human); 0 (STAT6 Transcription Factor); 0 (STAT6 protein, human); 207137-56-2 (Interleukin-4); 9006-59-1 (Ovalbumin); EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases); EC 1.14.11.- (KDM6B protein, human) [Em] Mês de entrada: 1604 [Cu] Atualização por classe: 161125 [Lr] Data última revisão: 161125 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150509 [St] Status: MEDLINE [do] DOI: 10.1002/ar.23172

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[PMID]: 25616164 [Au] Autor: Lu CS; Hung AF; Lin CJ; Chen JB; Chen C; Shiung YY; Tsai CY; Chang TW [Ad] Endereço: Genomics Research Center, Academia Sinica, Taipei, Taiwan. [Ti] Título: Generating allergen-specific human IgEs for immunoassays by employing human ε gene knockin mice. [So] Source: Allergy;70(4):384-90, 2015 Apr. [Is] ISSN: 1398-9995 [Cp] País de publicação: Denmark [La] Idioma: eng [Ab] Resumo: BACKGROUND: Antigen-specific human IgEs are important reagents in immunoassays to quantify antigen-specific IgEs in allergic patients, but they are not easy to prepare. METHODS: We constructed a knockin homozygous mouse strain, referred to as HεκKI strain, whose gene segment encoding γ1 constant region has been replaced by that encoding human ε constant region and gene segment encoding κ constant region replaced by that encoding human κ constant region. The mice were tested for their ability to produce antigen-specific chimeric human IgE (with mouse variable regions) upon the immunization with ovalbumin and papain. Subsequently, the spleen cells from the immunized mice were used as the source of B cells for the preparation of hybridomas, which secreted monoclonal human IgE antibodies specific for the antigens. RESULTS: The HεκKI mice expressed human IgE (ε, κ) in serum at levels 10- to 30-fold higher than those of mouse IgE. Upon immunization with an antigen, the mice yielded splenic B cells for preparing hybridomas that secrete chimeric human IgE specific for the antigen. Purified IgEs from those hybridomas could activate a basophilic cell line to undergo degranulation upon the stimulation with their respective antigens. CONCLUSIONS: We have developed a human ε gene and κ gene knockin mouse strain, which is useful for producing various antigen-specific chimeric human IgEs for potential use as standards in immunoassays. [Mh] Termos MeSH primário: Alérgenos/imunologia Imunoensaio Imunoglobulina E/imunologia Cadeias épsilon de Imunoglobulina/genética [Mh] Termos MeSH secundário: Animais Anticorpos Monoclonais/imunologia Anticorpos Monoclonais Humanizados/imunologia Especificidade de Anticorpos Antígenos/imunologia Basófilos/imunologia Degranulação Celular/imunologia Ensaio de Imunoadsorção Enzimática Ordem dos Genes Marcação de Genes Loci Gênicos Seres Humanos Hibridomas Hipersensibilidade/diagnóstico Hipersensibilidade/genética Hipersensibilidade/imunologia Imunização Imunoglobulina E/sangue Cadeias Pesadas de Imunoglobulinas/genética Cadeias Leves de Imunoglobulina/genética Imunoglobulinas/sangue Imunoglobulinas/imunologia Camundongos Camundongos Transgênicos [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Allergens); 0 (Antibodies, Monoclonal); 0 (Antibodies, Monoclonal, Humanized); 0 (Antigens); 0 (Immunoglobulin Heavy Chains); 0 (Immunoglobulin Light Chains); 0 (Immunoglobulin epsilon-Chains); 0 (Immunoglobulins); 37341-29-0 (Immunoglobulin E) [Em] Mês de entrada: 1512 [Cu] Atualização por classe: 150330 [Lr] Data última revisão: 150330 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150124 [St] Status: MEDLINE [do] DOI: 10.1111/all.12572

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[PMID]: 24532577 [Au] Autor: Janssen E; Ozcan E; Liadaki K; Jabara HH; Manis J; Ullas S; Akira S; Fitzgerald KA; Golenbock DT; Geha RS [Ad] Endereço: Division of Immunology, Boston Children's Hospital, Boston, MA 02115; [Ti] Título: TRIF signaling is essential for TLR4-driven IgE class switching. [So] Source: J Immunol;192(6):2651-8, 2014 Mar 15. [Is] ISSN: 1550-6606 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The TLR4 ligand LPS causes mouse B cells to undergo IgE and IgG1 isotype switching in the presence of IL-4. TLR4 activates two signaling pathways mediated by the adaptor molecules MyD88 and Toll/IL-IR domain-containing adapter-inducing IFN-ß (TRIF)-related adaptor molecule (TRAM), which recruits TRIF. Following stimulation with LPS plus IL-4, Tram(-/-) and Trif(-/-) B cells completely failed to express Cε germline transcripts (GLT) and secrete IgE. In contrast, Myd88(-/-) B cells had normal expression of Cε GLT but reduced IgE secretion in response to LPS plus IL-4. Following LPS plus IL-4 stimulation, Cγ1 GLT expression was modestly reduced in Tram(-/-) and Trif(-/-) B cells, whereas Aicda expression and IgG1 secretion were reduced in Tram(-/-), Trif(-/-), and Myd88(-/-) B cells. B cells from all strains secreted normal amounts of IgE and IgG1 in response to anti-CD40 plus IL-4. Following stimulation with LPS plus IL-4, Trif(-/-) B cells failed to sustain NF-κB p65 nuclear translocation beyond 3 h and had reduced binding of p65 to the Iε promoter. Addition of the NF-κB inhibitor, JSH-23, to wild-type B cells 15 h after LPS plus IL-4 stimulation selectively blocked Cε GLT expression and IgE secretion but had little effect on Cγ1 GLT expression and IgG secretion. These results indicate that sustained activation of NF-κB driven by TRIF is essential for LPS plus IL-4-driven activation of the Cε locus and class switching to IgE. [Mh] Termos MeSH primário: Proteínas Adaptadoras de Transporte Vesicular/imunologia Switching de Imunoglobulina/imunologia Imunoglobulina E/imunologia Transdução de Sinais/imunologia Receptor 4 Toll-Like/imunologia [Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transporte Vesicular/genética Proteínas Adaptadoras de Transporte Vesicular/metabolismo Animais Linfócitos B/efeitos dos fármacos Linfócitos B/imunologia Linfócitos B/metabolismo Sobrevivência Celular/efeitos dos fármacos Sobrevivência Celular/genética Sobrevivência Celular/imunologia Citidina Desaminase/genética Citidina Desaminase/imunologia Citidina Desaminase/metabolismo Immunoblotting Switching de Imunoglobulina/efeitos dos fármacos Imunoglobulina E/genética Imunoglobulina E/metabolismo Imunoglobulina G/genética Imunoglobulina G/imunologia Imunoglobulina G/metabolismo Cadeias épsilon de Imunoglobulina/genética Cadeias épsilon de Imunoglobulina/imunologia Cadeias épsilon de Imunoglobulina/metabolismo Cadeias gama de Imunoglobulina/genética Cadeias gama de Imunoglobulina/imunologia Cadeias gama de Imunoglobulina/metabolismo Interleucina-4/imunologia Interleucina-4/farmacologia Lipopolissacarídeos/imunologia Lipopolissacarídeos/farmacologia Camundongos Camundongos da Linhagem 129 Camundongos Endogâmicos BALB C Camundongos Endogâmicos C57BL Camundongos Knockout Fator 88 de Diferenciação Mieloide/genética Fator 88 de Diferenciação Mieloide/imunologia Fator 88 de Diferenciação Mieloide/metabolismo Fenilenodiaminas/imunologia Fenilenodiaminas/farmacologia Receptores de Interleucina/genética Receptores de Interleucina/imunologia Receptores de Interleucina/metabolismo Reação em Cadeia da Polimerase Via Transcriptase Reversa Transdução de Sinais/efeitos dos fármacos Transdução de Sinais/genética Receptor 4 Toll-Like/agonistas Receptor 4 Toll-Like/metabolismo Fator de Transcrição RelA/antagonistas & inibidores Fator de Transcrição RelA/imunologia Fator de Transcrição RelA/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (4-methyl-N1-(3-phenylpropyl)benzene-1,2-diamine); 0 (Adaptor Proteins, Vesicular Transport); 0 (Immunoglobulin G); 0 (Immunoglobulin epsilon-Chains); 0 (Immunoglobulin gamma-Chains); 0 (Lipopolysaccharides); 0 (Myd88 protein, mouse); 0 (Myeloid Differentiation Factor 88); 0 (Phenylenediamines); 0 (Receptors, Interleukin); 0 (TICAM-1 protein, mouse); 0 (TIRP protein, mouse); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4); 0 (Transcription Factor RelA); 207137-56-2 (Interleukin-4); 37341-29-0 (Immunoglobulin E); EC 3.5.4.- (AICDA (activation-induced cytidine deaminase)); EC 3.5.4.5 (Cytidine Deaminase) [Em] Mês de entrada: 1405 [Cu] Atualização por classe: 161019 [Lr] Data última revisão: 161019 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 140218 [St] Status: MEDLINE [do] DOI: 10.4049/jimmunol.1300909

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[PMID]: 24019479 [Au] Autor: Misaghi S; Senger K; Sai T; Qu Y; Sun Y; Hamidzadeh K; Nguyen A; Jin Z; Zhou M; Yan D; Lin WY; Lin Z; Lorenzo MN; Sebrell A; Ding J; Xu M; Caplazi P; Austin CD; Balazs M; Roose-Girma M; DeForge L; Warming S; Lee WP; Dixit VM; Zarrin AA [Ad] Endereço: Genentech, Inc., South San Francisco, CA 94080. [Ti] Título: Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination. [So] Source: Proc Natl Acad Sci U S A;110(39):15770-5, 2013 Sep 24. [Is] ISSN: 1091-6490 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Preceding antibody constant regions are switch (S) regions varying in length and repeat density that are targets of activation-induced cytidine deaminase. We asked how participating S regions influence each other to orchestrate rearrangements at the IgH locus by engineering mice in which the weakest S region, Sε, is replaced with prominent recombination hotspot Sµ. These mice produce copious polyclonal IgE upon challenge, providing a platform to study IgE biology and therapeutic interventions. The insertion enhances ε germ-line transcript levels, shows a preference for direct vs. sequential switching, and reduces intraswitch recombination events at native Sµ. These results suggest that the sufficiency of Sµ to mediate IgH rearrangements may be influenced by context-dependent cues. [Mh] Termos MeSH primário: Switching de Imunoglobulina/genética Imunoglobulina E/metabolismo Recombinação Genética [Mh] Termos MeSH secundário: Alelos Animais Linfócitos B/metabolismo Técnicas de Introdução de Genes Marcação de Genes Loci Gênicos/genética Células Germinativas/metabolismo Hibridomas Cadeias épsilon de Imunoglobulina/genética Cadeias mu de Imunoglobulina/genética Ativação Linfocitária/genética Camundongos Modelos Animais RNA Mensageiro/genética RNA Mensageiro/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Immunoglobulin epsilon-Chains); 0 (Immunoglobulin mu-Chains); 0 (RNA, Messenger); 37341-29-0 (Immunoglobulin E) [Em] Mês de entrada: 1312 [Cu] Atualização por classe: 150422 [Lr] Data última revisão: 150422 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 130911 [St] Status: MEDLINE [do] DOI: 10.1073/pnas.1221661110

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[PMID]: 23589612 [Au] Autor: Audzevich T; Pearce G; Breucha M; Günal G; Jessberger R [Ad] Endereço: Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, 01307 Dresden, Germany. [Ti] Título: Control of the STAT6-BCL6 antagonism by SWAP-70 determines IgE production. [So] Source: J Immunol;190(10):4946-55, 2013 May 15. [Is] ISSN: 1550-6606 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Asthma and allergies are major health concerns in which Ig isotype E plays a pivotal role. Ag-bound IgE drives mast cells and basophils into exocytosis, thereby promoting allergic and potentially anaphylactic reactions. The importance of tightly regulated IgE production is underscored by severe immunological conditions in humans with elevated IgE levels. Cytokines direct IgH class-switching to a particular isotype by initiation of germline transcription (GLT) from isotype-specific intronic (I) promoters. The switch to IgE depends on IL-4, which stimulates GLT of the Iε promoter, but is specifically and strongly impaired in Swap-70(-/-) mice. Although early events in IL-4 signal transduction (i.e., activation of the JAK/STAT6 pathway) do not require SWAP-70, SWAP-70 deficiency results in impaired Iε GLT. The affinity of STAT6 to chromatin is reduced in absence of SWAP-70. Chromatin immunoprecipitation revealed that SWAP-70 binds to Iε and is required for association of STAT6 with Iε. BCL6, known to antagonize STAT6 particularly at Iε, is increased on Iε in absence of SWAP-70. Other promoters bound by BCL6 and STAT6 were found unaffected. We conclude that SWAP-70 controls IgE production through regulation of the antagonistic STAT6 and BCL6 occupancy of Iε. The identification of this mechanism opens new avenues to inhibit allergic reactions triggered by IgE. [Mh] Termos MeSH primário: Proteínas de Ligação a DNA/metabolismo Fatores de Troca do Nucleotídeo Guanina/metabolismo Switching de Imunoglobulina/imunologia Imunoglobulina E/biossíntese Proteínas Nucleares/metabolismo Fator de Transcrição STAT6/metabolismo [Mh] Termos MeSH secundário: Células 3T3 Animais Linfócitos B/imunologia Células Cultivadas Cromatina/metabolismo Proteínas de Ligação a DNA/genética Fatores de Troca do Nucleotídeo Guanina/genética Hipersensibilidade/imunologia Switching de Imunoglobulina/genética Cadeias Pesadas de Imunoglobulinas/imunologia Cadeias épsilon de Imunoglobulina/metabolismo Interleucina-4/metabolismo Camundongos Camundongos Endogâmicos C57BL Camundongos Knockout Antígenos de Histocompatibilidade Menor Proteínas Nucleares/genética Regiões Promotoras Genéticas Proteínas Proto-Oncogênicas c-bcl-6 Transdução de Sinais/imunologia Transcrição Genética [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Bcl6 protein, mouse); 0 (Chromatin); 0 (DNA-Binding Proteins); 0 (Guanine Nucleotide Exchange Factors); 0 (Immunoglobulin Heavy Chains); 0 (Immunoglobulin epsilon-Chains); 0 (Minor Histocompatibility Antigens); 0 (Nuclear Proteins); 0 (Proto-Oncogene Proteins c-bcl-6); 0 (STAT6 Transcription Factor); 0 (Stat6 protein, mouse); 0 (Swap70 protein, mouse); 207137-56-2 (Interleukin-4); 37341-29-0 (Immunoglobulin E) [Em] Mês de entrada: 1307 [Cu] Atualização por classe: 161125 [Lr] Data última revisão: 161125 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 130417 [St] Status: MEDLINE [do] DOI: 10.4049/jimmunol.1203014

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[PMID]: 23460965 [Au] Autor: Liu ZC; Zhao LJ; Zhang YF; Shi HL; Xie Y [Ad] Endereço: College of Pharmaceutical Sciences of Hebei University, Key Laboratory for Drug Quality Control and Analysis of Hebei Province. liuzc@hbu.edu.cn [Ti] Título: [Screening and characterization of aptamers of Cepsilon3-Cepsilon4 protein]. [So] Source: Yao Xue Xue Bao;47(12):1605-11, 2012 Dec. [Is] ISSN: 0513-4870 [Cp] País de publicação: China [La] Idioma: chi [Ab] Resumo: In order to obtain nucleotides aptamers bind to IgE, 80 bp nucleotides single-stranded DNA library containing 40 random nucleotides was designed and synthesized. Oligonucleotides that bind to human Cepsilon3-Cepsilon4 protein were isolated from ssDNA pools by the systematic evolution of ligands by exponential enrichment (SELEX) method using nitrocellulose filters as screening medium. Through the optimization of critical PCR and asymmetric PCR parameters including annealing temperature, cycles, and molar ratios of target protein and ssDNA etc, a suitable screening system was established. The aptamers of Cepsilon3-Cepsilon4 protein with high affinity and high specificity were identified by ELISA with biotin-streptavidin-horseradish peroxidase system, and its primary sequence and second structure were analyzed by DNAMAN package and DNA folding sever after being cloned and sequenced. Moreover, target protein was bound to one aptamer and another aptamer modified with biotion together forming a sandwich-like complex, which was captured in microwell to detect IgE concentration using the optimal combination in the sandwich method named enzyme-linked aptamers sorption assay (ELASA). The method could be used for the quantitative detection of human IgE, and whose sensitivity reached to 120 ng x mL(-1). [Mh] Termos MeSH primário: Aptâmeros de Nucleotídeos/química DNA de Cadeia Simples Cadeias épsilon de Imunoglobulina/química [Mh] Termos MeSH secundário: Aptâmeros de Nucleotídeos/genética Aptâmeros de Nucleotídeos/isolamento & purificação Sequência de Bases DNA de Cadeia Simples/química Seres Humanos Cadeias épsilon de Imunoglobulina/genética Oligonucleotídeos/química Técnica de Seleção de Aptâmeros/métodos Sensibilidade e Especificidade [Pt] Tipo de publicação: ENGLISH ABSTRACT; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Aptamers, Nucleotide); 0 (DNA, Single-Stranded); 0 (Immunoglobulin epsilon-Chains); 0 (Oligonucleotides) [Em] Mês de entrada: 1312 [Cu] Atualização por classe: 130305 [Lr] Data última revisão: 130305 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 130306 [St] Status: MEDLINE

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[PMID]: 22750228 [Au] Autor: Chowdhury PS; Chen Y; Yang C; Cook KE; Nyborg AC; Ettinger R; Herbst R; Kiener PA; Wu H [Ad] Endereço: Department of Antibody Discovery and Protein Engineering, MedImmune, LLC, Gaithersburg, MD 20878, USA. chowdhuryp@medimmune.com [Ti] Título: Targeting the junction of CÉ›mX and É›-migis for the specific depletion of mIgE-expressing B cells. [So] Source: Mol Immunol;52(3-4):279-88, 2012 Oct. [Is] ISSN: 1872-9142 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Monoclonal antibodies targeting the extracellular region of the human IgE heavy chain membrane-tethering domain have been proposed for treating allergies caused by hyperproliferative monoclonal expansion of IgE-producing B cells. Antibodies against this target are expected to deplete membrane IgE (mIgE) displaying B cells and leave B cells of other immunoglobulin isotypes intact. Because of alternative splicing, the mIgE heavy chain has two isoforms that differ in their membrane-proximal segment. In the long isoform, the CH4 domain is followed by a 67-amino acid-long extracellular portion. Out of these 67 amino acids, the first 52 amino acids following the CH4 domain constitute the CÉ›mX segment while the rest of the 15 amino acids immediately adjacent to the membrane constitute the É›-migis. In the short isoform the CÉ›mX segment is absent and the CH4 domain is followed only by the 15-amino acid-long É›-migis segment. Using antibodies derived from a phage display library, we investigated: (1) É›-migis and (2) the junction of CÉ›mX and É›-migis (CÉ›mX.migis), as potential therapeutic antibody targets. Our results indicate that antibodies obtained from our phage library that target É›-migis bind to a variety of human cells irrespective of mIgE expression, possibly due to homology between É›-migis and a region of phosphoinositide-binding protein (ARAP3). In contrast, antibodies specific for the CÉ›mX.migis junctional region, bound specifically to transfected and primary B cells expressing human mIgE and elicited antibody-dependent cellular cytotoxicity and reduction in IgE production. These antibodies did not bind secreted IgE or the mIgE isoform in which CÉ›mX is absent. These results suggest that CÉ›mX.migis junctional region is a promising antibody target and the human antibodies we describe warrant further evaluation. [Mh] Termos MeSH primário: Anticorpos Anti-Idiotípicos/imunologia Linfócitos B/imunologia Imunoglobulina E/imunologia Cadeias épsilon de Imunoglobulina/imunologia Receptores de Antígenos de Linfócitos B/imunologia [Mh] Termos MeSH secundário: Anticorpos Monoclonais Citotoxicidade Celular Dependente de Anticorpos Linfócitos B/metabolismo Linhagem Celular Membrana Celular/imunologia Proliferação Celular Células HEK293 Seres Humanos Imunoglobulina E/biossíntese Fosfatidilinositóis/imunologia Isoformas de Proteínas/imunologia Receptores de Antígenos de Linfócitos B/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Anti-Idiotypic); 0 (Antibodies, Monoclonal); 0 (Immunoglobulin epsilon-Chains); 0 (Phosphatidylinositols); 0 (Protein Isoforms); 0 (Receptors, Antigen, B-Cell); 37341-29-0 (Immunoglobulin E) [Em] Mês de entrada: 1210 [Cu] Atualização por classe: 121105 [Lr] Data última revisão: 121105 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 120704 [St] Status: MEDLINE [do] DOI: 10.1016/j.molimm.2012.06.004

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[PMID]: 22143888 [Au] Autor: Wesemann DR; Magee JM; Boboila C; Calado DP; Gallagher MP; Portuguese AJ; Manis JP; Zhou X; Recher M; Rajewsky K; Notarangelo LD; Alt FW [Ad] Endereço: Program in Cellular and Molecular Medicine and Immune Disease Institute, Children's Hospital Boston, MA 02115, USA. [Ti] Título: Immature B cells preferentially switch to IgE with increased direct Sµ to Sε recombination. [So] Source: J Exp Med;208(13):2733-46, 2011 Dec 19. [Is] ISSN: 1540-9538 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cµ (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from Cµ to Cγ1 (IgG1) and Cε (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although Cε CSR can occur directly from Cµ, most mature peripheral B cells undergo CSR to Cε indirectly, namely from Cµ to Cγ1, and subsequently to Cε. Physiological mechanisms that influence CSR to Cγ1 versus Cε are incompletely understood. In this study, we report a role for B cell developmental maturity in IgE CSR. Based in part on a novel flow cytometric IgE CSR assay, we show that immature B cells preferentially switch to IgE versus IgG1 through a mechanism involving increased direct CSR from Cµ to Cε. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation. [Mh] Termos MeSH primário: Linfócitos B/imunologia Switching de Imunoglobulina/fisiologia Imunoglobulina E/imunologia Cadeias épsilon de Imunoglobulina/imunologia Cadeias mu de Imunoglobulina/imunologia Recombinação Genética/fisiologia [Mh] Termos MeSH secundário: Animais Imunodeficiência de Variável Comum/genética Imunodeficiência de Variável Comum/imunologia Imunoglobulina E/genética Imunoglobulina G/genética Imunoglobulina G/imunologia Cadeias épsilon de Imunoglobulina/genética Cadeias mu de Imunoglobulina/genética Camundongos Camundongos Knockout [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Immunoglobulin G); 0 (Immunoglobulin epsilon-Chains); 0 (Immunoglobulin mu-Chains); 37341-29-0 (Immunoglobulin E) [Em] Mês de entrada: 1202 [Cu] Atualização por classe: 171010 [Lr] Data última revisão: 171010 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 111207 [St] Status: MEDLINE [do] DOI: 10.1084/jem.20111155

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MEDLINE

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[PMID]: 21106524 [Au] Autor: Dong L; Zhang X; Fu X; Zhang X; Gao X; Zhu M; Wang X; Yang Z; Jensen ON; Saarikettu J; Yao Z; Silvennoinen O; Yang J [Ad] Endereço: Department of Immunology, Basic Medical College, Tianjin Medical University, Heping District, Qixiangtai Road No. 22, Tianjin 300070, China. [Ti] Título: PTB-associated splicing factor (PSF) functions as a repressor of STAT6-mediated Ig epsilon gene transcription by recruitment of HDAC1. [So] Source: J Biol Chem;286(5):3451-9, 2011 Feb 04. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Regulation of transcription requires cooperation between sequence-specific transcription factors and numerous coregulatory proteins. In IL-4/IL-13 signaling several coactivators for STAT6 have been identified, but the molecular mechanisms of STAT6-mediated gene transcription are still not fully understood. Here we identified by proteomic approach that the PTB-associated splicing factor (PSF) interacts with STAT6. In intact cells the interaction was observed only after IL-4 stimulation. The IL-4-induced tyrosine phosphorylation of both STAT6 and PSF is a prerequisite for the efficient association of the two proteins. Functional analysis demonstrated that ectopic expression of PSF resulted in inhibition of STAT6-mediated transcriptional activation and mRNA expression of the Igε germline heavy chain gene, whereas knockdown of PSF increased the STAT6-mediated responses. PSF recruited histone deacetylase 1 (HDAC1) to the STAT6 transcription complex, which resulted in reduction of H3 acetylation at the promoter regions of Ig heavy chain germline Igε and inhibition of STAT6-mediated transcription. In addition, the HDACs inhibitor trichostatin A (TSA) enhanced H3 acetylation, and reverted the PSF-mediated transcriptional repression of Igε gene transcription. In summary, these results identify PSF as a repressor of STAT6-mediated transcription that functions through recruitment of HDAC to the STAT6 transcription complex, and delineates a novel regulatory mechanism of IL-4 signaling that may have implications in the pathogenesis of allergic diseases and pharmacological HDAC inhibition in lymphomas. [Mh] Termos MeSH primário: Histona Desacetilase 1/metabolismo Cadeias épsilon de Imunoglobulina/genética Proteínas de Ligação a RNA/fisiologia Fator de Transcrição STAT6/fisiologia Transcrição Genética [Mh] Termos MeSH secundário: Genes de Imunoglobulinas Células HeLa Seres Humanos Interleucina-4/farmacologia Fator de Processamento Associado a PTB Ligação Proteica/efeitos dos fármacos Mapeamento de Interação de Proteínas Transporte Proteico Proteínas de Ligação a RNA/metabolismo Proteínas Repressoras Ativação Transcricional [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Immunoglobulin epsilon-Chains); 0 (PTB-Associated Splicing Factor); 0 (RNA-Binding Proteins); 0 (Repressor Proteins); 0 (STAT6 Transcription Factor); 0 (STAT6 protein, human); 207137-56-2 (Interleukin-4); EC 3.5.1.98 (Histone Deacetylase 1) [Em] Mês de entrada: 1103 [Cu] Atualização por classe: 161125 [Lr] Data última revisão: 161125 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 101126 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M110.168377

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