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1.
Am J Pathol ; 189(4): 762-772, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30711489

RESUMO

Increased angiogenesis is a characteristic feature of remodeling in asthmatic airways and stems from the imbalance between pro-angiogenic and anti-angiogenic factors. Surprisingly, the factors regulating this process in allergic asthma are poorly defined. Previously, we showed an important role of semaphorins 3E (Sema3E) in growth factor-induced airway smooth muscle proliferation and migration in vitro, and in down-regulating airway inflammation, T helper 2/T helper 17 cytokine response, mucus cell hyperplasia, and airway hyperresponsiveness in vivo. However, the role of Sema3E in airway angiogenesis is not fully understood. Here, we investigated the role of Sema3E in airway angiogenesis using a house dust mite (HDM) murine model of allergic asthma. Intranasal treatment with recombinant Sema3E significantly reduced the expression of angiogenesis markers within the airways of HDM-challenged mice compared with untreated mice. HDM-induced expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 protein were diminished substantially on Sema3E treatment. Interestingly, Sema3E-treated mice showed an enhanced expression of the negative regulator of angiogenesis, soluble VEGF receptor 1, compared with the untreated mice. These events were reversed in Sema3E-deficient mice at baseline or on HDM challenge. Taken together, this study provides the first evidence that Sema3E modulates angiogenesis in allergic asthmatic airways via modulating pro- and anti-angiogenic factors.


Assuntos
Asma/prevenção & controle , Proteínas do Citoesqueleto/fisiologia , Modelos Animais de Doenças , Inflamação/prevenção & controle , Proteínas de Membrana/fisiologia , Neovascularização Patológica/prevenção & controle , Pyroglyphidae/patogenicidade , Hipersensibilidade Respiratória/prevenção & controle , Remodelação das Vias Aéreas , Alérgenos/imunologia , Indutores da Angiogênese/imunologia , Indutores da Angiogênese/metabolismo , Animais , Asma/etiologia , Asma/patologia , Feminino , Inflamação/etiologia , Inflamação/patologia , Camundongos , Camundongos Knockout , Neovascularização Patológica/etiologia , Neovascularização Patológica/patologia , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/patologia
2.
Am J Physiol Lung Cell Mol Physiol ; 315(5): L787-L798, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30188746

RESUMO

Allergic asthma is a major cause of morbidity in both pediatric and adult patients. Recent research has highlighted the role of hyaluronan (HA), an extracellular matrix glycosaminoglycan, in asthma pathogenesis. Experimental allergic airway inflammation and clinical asthma are associated with an increase of shorter fragments of HA (sHA), which complex with inter-α-inhibitor heavy chains (HCs) and induce inflammation and airway hyperresponsiveness (AHR). Importantly, the effects of sHA can be antagonized by the physiological counterpart high molecular weight HA (HMWHA). We used a mouse model of house dust mite-induced allergic airway inflammation and demonstrated that instilled HMWHA ameliorated allergic airway inflammation and AHR, even when given after the establishment of allergic sensitization and after challenge exposures. Furthermore, instilled HMWHA reduced the development of HA-HC complexes and the activation of Rho-associated, coiled-coil containing protein kinase 2. We conclude that airway application of HMWHA is a potential treatment for allergic airway inflammation.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Modelos Animais de Doenças , Ácido Hialurônico/administração & dosagem , Inflamação/prevenção & controle , Pyroglyphidae/patogenicidade , Hipersensibilidade Respiratória/prevenção & controle , Animais , Feminino , Inflamação/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Hipersensibilidade Respiratória/etiologia
3.
Am J Physiol Lung Cell Mol Physiol ; 315(4): L553-L562, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29975102

RESUMO

Eosinophilia (EOS) is an important component of airway inflammation and hyperresponsiveness in allergic reactions including those leading to asthma. Although cigarette smoking (CS) is a significant contributor to long-term adverse outcomes in these lung disorders, there are also the curious reports of its ability to produce acute suppression of inflammatory responses including EOS through poorly understood mechanisms. One possibility is that proinflammatory processes are suppressed by nicotine in CS acting through nicotinic receptor α7 (α7). Here we addressed the role of α7 in modulating EOS with two mouse models of an allergic response: house dust mites (HDM; Dermatophagoides sp.) and ovalbumin (OVA). The influence of α7 on EOS was experimentally resolved in wild-type mice or in mice in which a point mutation of the α7 receptor (α7E260A:G) selectively restricts normal signaling of cellular responses. RNA analysis of alveolar macrophages and the distal lung epithelium indicates that normal α7 function robustly impacts gene expression in the epithelium to HDM and OVA but to different degrees. Notable was allergen-specific α7 modulation of Ccl11 and Ccl24 (eotaxins) expression, which was enhanced in HDM but suppressed in OVA EOS. CS suppressed EOS induced by both OVA and HDM, as well as the inflammatory genes involved, regardless of α7 genotype. These results suggest that EOS in response to HDM or OVA is through signaling pathways that are modulated in a cell-specific manner by α7 and are distinct from CS suppression.


Assuntos
Fumar Cigarros/imunologia , Pulmão/efeitos dos fármacos , Ovalbumina/toxicidade , Eosinofilia Pulmonar/prevenção & controle , Pyroglyphidae/patogenicidade , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Citocinas/metabolismo , Feminino , Pulmão/imunologia , Pulmão/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Eosinofilia Pulmonar/etiologia , Eosinofilia Pulmonar/metabolismo , Eosinofilia Pulmonar/patologia , Receptor Nicotínico de Acetilcolina alfa7/genética
4.
J Leukoc Biol ; 103(5): 897-908, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29393977

RESUMO

Airway epithelial cells play a significant role in the pathogenesis of asthma. Although the structural and functional defects of airway epithelial cells have been postulated to increase asthma susceptibility and exacerbate asthma severity, the mechanism and implication of these defects remain uncertain. Integrin ß4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. In this study, we demonstrated that ITGB4 deficiency leads to severe allergy-induced airway inflammation and airway hyper-responsiveness (AHR) in mice. After house dust mite (HDM) challenge, epithelial cell-specific ITGB4-deleted mice showed increased lymphocyte, eosinophil, and neutrophil infiltration into lung compared with that of the wild-type mice. ITGB4 deficiency also resulted in increased expression of the Th2 cytokine IL-4, IL-13, and the Th17 cytokine IL-17A in the lung tissue and in the T cells after HDM challenge. The aggravated inflammation in ITGB4 defect mice was partly caused by enhanced disrupted epithelial barrier integrity after HDM stress, which induced the increased thymic stromal lymphopoietin secretion from airway epithelial cells. This study therefore demonstrates that ITGB4 plays a pivotal role in containing allergen-mediated lung inflammation and airway hyper-responsiveness in allergic asthma.


Assuntos
Alérgenos/efeitos adversos , Integrina beta4/fisiologia , Pneumonia/etiologia , Pyroglyphidae/patogenicidade , Hipersensibilidade Respiratória/etiologia , Linfócitos T/imunologia , Animais , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/patologia , Hipersensibilidade Respiratória/patologia
5.
Int J Immunogenet ; 44(2): 62-70, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28181414

RESUMO

The prevalence of allergic rhinitis (AR) and asthma has been increasing, and the comorbidity rates of these diseases are very high. Here, 176 AR patients, 124 patients with comorbid AR and asthma (AR-A) and 206 healthy Chinese children as controls were included in a case-control study. Six single-nucleotide polymorphisms (SNPs), miR-146a (rs2910164, rs57095329 and rs6864584), miR-196a2 (rs11614913), miR-499 (rs3746444) and miR-149 (rs2292832), were genotyped. The prevalence of homozygous miR-149 (rs2292832) CC genotype and C allele were considerably increased in AR and AR-A patients, compared with the controls. AR-A group showed higher frequencies of CC genotype and C allele of rs2292832 than AR group. No significant difference in the genotypic and allelic frequencies of other miRNA SNPs was found between the groups. MiR-149 levels in peripheral blood mononuclear cells (PBMCs) were significantly lower in CC (variant type) cases compared with TT (wild-type) cases. In further experiments, PBMCs obtained from the healthy controls with CC, CT and TT genotypes were stimulated by house dust mite extracts, which led to a significant decrease in the levels of miR-149 in PBMCs obtained from CC and TT individuals. This decrease was more pronounced in CC compared with TT cases. Our results demonstrate that miR-149 rs2292832 variant is not only strongly associated with AR and AR-A, but it may lead to an increase in the susceptibility to allergies following the stimulation with an allergen, through the changes in miR149 expression. Additionally, AR patients with CC genotypes were shown to be more susceptible to asthma.


Assuntos
Asma/genética , MicroRNAs/genética , Rinite Alérgica/genética , Adolescente , Alelos , Animais , Asma/complicações , Asma/patologia , Criança , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Leucócitos Mononucleares/imunologia , Masculino , MicroRNAs/biossíntese , Polimorfismo de Nucleotídeo Único , Pyroglyphidae/genética , Pyroglyphidae/patogenicidade , Rinite Alérgica/complicações , Rinite Alérgica/imunologia , Rinite Alérgica/patologia , Fatores de Risco
6.
Allergol. immunopatol ; 45(1): 11-17, ene.-feb. 2017. tab, graf
Artigo em Inglês | IBECS | ID: ibc-158969

RESUMO

Background: House dust mites are a ubiquitous air allergen in the human habitat. It has been shown that exposure to them is a fundamental factor in sensitisation and development of atopic disease. The objective of the study was to analyse changes in sensitisation to Dermatophagoides pteronyssinus (Der p.) in children treated in a tertiary level care hospital in Mexico City for a period of 11 years and compare with other studies carried out in Mexico. Methods: A retrospective study was performed at the Hospital Infantil de México Federico Gómez (HIMFG). Information was gathered from skin tests for Der p. performed in the Allergy Laboratory from January 2004 to April 2015. Patients 2-18 years old who presented for examination of some type of allergic condition and who had immediate hypersensitivity tests to Der p. were included in the study. Results were compared with prior reports from other institutions. Descriptive analysis and 2 statistics were used. Results: A total of 8794 patients were included in the study; 49.3% of the tests (95% CI 48-50) were positive for Der p. The percentage of monosensitised to mites was 2.7% for Der p. (95% CI 2-3). A significant difference was found between the results of older patients and those <6 years old. The frequency of sensitisation had a tendency to decrease during the 11 years analysed in all age groups. Conclusions and clinical relevance: The frequency of sensitisation to Der p. increased with age until reaching adolescence. In the last 11 years a decrease in sensitisation to this air allergen was observed (AU)


No disponible


Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Pyroglyphidae/patogenicidade , Hipersensibilidade Respiratória/imunologia , Apresentação Cruzada/imunologia , Poeira/análise , /análise , Estudos Retrospectivos , Testes de Irritação da Pele , Distribuição por Idade
7.
Theranostics ; 7(2): 377-389, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28042341

RESUMO

Although angiogenesis is a hallmark feature of asthmatic inflammatory responses, therapeutic anti-angiogenesis interventions have received little attention. Objective: Assess the effectiveness of anti-angiogenic Sn2 lipase-labile prodrugs delivered via αvß3-micellar nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Results: Anti-neovascular effectiveness of αvß3-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0.01) in the upper airways/bronchi of HDM rats using simultaneous 19F/1H MR neovascular imaging, which was corroborated by adjunctive fluorescent microscopy. Micelles without a drug payload (αvß3-No-Drug) served as a carrier-only control. Morphometric measurements of HDM rat airway size (perimeter) and vessel number at 21d revealed classic vascular expansion in control rats but less vascularity (p<0.001) after the anti-angiogenic nanotherapies. CD31 RNA expression independently corroborated the decrease in airway microvasculature. Methacholine (MCh) induced respiratory system resistance (Rrs) was high in the HDM rats receiving αvß3-No-Drug micelles while αvß3-Dxtl-PD or αvß3-Fum-PD micelles markedly and equivalently attenuated airway hyper-responsiveness and improved airway compliance. Total inflammatory BAL cells among HDM challenged rats did not differ with treatment, but αvß3+ macrophages/monocytes were significantly reduced by both nanotherapies (p<0.001), most notably by the αvß3-Dxtl-PD micelles. Additionally, αvß3-Dxtl-PD decreased BAL eosinophil and αvß3+ CD45+ leukocytes relative to αvß3-No-Drug micelles, whereas αvß3-Fum-PD micelles did not. Conclusion: These results demonstrate the potential of targeted anti-angiogenesis nanotherapy to ameliorate the inflammatory hallmarks of asthma in a clinically relevant rodent model.


Assuntos
Remodelação das Vias Aéreas , Inibidores da Angiogênese/administração & dosagem , Asma/tratamento farmacológico , Asma/patologia , Nanoestruturas/administração & dosagem , Animais , Asma/diagnóstico por imagem , Cicloexanos/administração & dosagem , Modelos Animais de Doenças , Docetaxel , Portadores de Fármacos/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Imagem por Ressonância Magnética , Microscopia de Fluorescência , Pró-Fármacos/administração & dosagem , Pyroglyphidae/patogenicidade , Ratos , Sesquiterpenos/administração & dosagem , Taxoides/administração & dosagem , Resultado do Tratamento
8.
Allergol. immunopatol ; 44(6): 580-593, nov.-dic. 2016. graf, tab
Artigo em Inglês | IBECS | ID: ibc-157881

RESUMO

Currently, mankind is afflicted with diversified health issues, allergies being a common, yet little understood malady. Allergies, the outcome of a baffled immune system encompasses myriad allergens and causes an array of health consequences, ranging from transient to recurrent and mild to fatal. Indoor allergy is a serious hypersensitivity in genetically-predisposed people, triggered by ingestion, inhalation or mere contact of allergens, of which mite and cockroaches are one of the most-represented constituents. Arduous to eliminate, these aeroallergens pose constant health challenges, mostly manifested as respiratory and dermatological inflammations, leading to further aggravations if unrestrained. Recent times have seen an unprecedented endeavour to understand the conformation of these allergens, their immune manipulative ploys and other underlying causes of pathogenesis, most importantly therapies. Yet a large section of vulnerable people is ignorant of these innocuous-looking immune irritants, prevailing around them, and continues to suffer. This review aims to expedite this field by a concise, informative account of seminal findings in the past few years, with particular emphasis on leading frontiers like genome-wide association studies (GWAS), epitope mapping, metabolomics etc. Drawbacks linked to current approaches and solutions to overcome them have been proposed (AU)


No disponible


Assuntos
Humanos , Pyroglyphidae/patogenicidade , Hipersensibilidade Respiratória/epidemiologia , Baratas/patogenicidade , Serina Proteases/imunologia , Mapeamento de Epitopos , Metabolômica/métodos , Estudo de Associação Genômica Ampla/métodos
9.
G3 (Bethesda) ; 6(9): 2857-65, 2016 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-27449512

RESUMO

Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene-environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design in which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics.


Assuntos
Asma/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Pyroglyphidae/patogenicidade , Locos de Características Quantitativas/genética , Alérgenos/administração & dosagem , Alérgenos/imunologia , Animais , Asma/genética , Asma/imunologia , Modelos Animais de Doenças , Interação Gene-Ambiente , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Hipersensibilidade/microbiologia , Imunização , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Cloreto de Metacolina/administração & dosagem , Camundongos , Pletismografia , Pyroglyphidae/genética , Pyroglyphidae/imunologia
10.
PLoS One ; 11(4): e0154001, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27101288

RESUMO

Asthma is the most common chronic disease in childhood. Although several therapeutic options are currently available to control the symptoms, many drugs have significant side effects and asthma remains an incurable disease. Microbial exposure in early life reduces the risk of asthma and several studies have suggested protective effects of Toll-like receptor (TLR) activation. We showed previously that modified mRNA provides a safe and efficient therapeutic tool for in vivo gene supplementation. Since current asthma drugs do not take patient specific immune and TLR backgrounds into consideration, treatment with tailored mRNA could be an attractive approach to account for the patient's individual asthma phenotype. Therefore, we investigated the effect of a preventative treatment with combinations of Tlr1, Tlr2 and Tlr6 mRNA in a House Dust Mite-induced mouse model of asthma. We used chemically modified mRNA which is-in contrast to conventional viral vectors-non-integrating and highly efficient in gene transfer. In our study, we found that treatment with either Tlr1/2 mRNA or Tlr2/6 mRNA, but not Tlr2 mRNA alone, resulted in better lung function as well as reduced airway inflammation in vivo. The present results point to a potentially protective effect of TLR heterodimers in asthma pathogenesis.


Assuntos
Asma/terapia , Modelos Animais de Doenças , RNA Mensageiro/genética , Receptores Toll-Like/genética , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Pyroglyphidae/patogenicidade
11.
J Leukoc Biol ; 100(1): 95-102, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26931576

RESUMO

In healthy lungs, many macrophages are characterized by IL-10 production, and few are characterized by expression of IFN regulatory factor 5 (formerly M1) or YM1 and/or CD206 (formerly M2), whereas in asthma, this balance shifts toward few producing IL-10 and many expressing IFN regulatory factor 5 or YM1/CD206. In this study, we tested whether redressing the balance by reinstating IL-10 production could prevent house dust mite-induced allergic lung inflammation. PGE2 was found to be the best inducer of IL-10 in macrophages in vitro. Mice were then sensitized and challenged to house dust mites during a 2 wk protocol while treated with PGE2 in different ways. Lung inflammation was assessed 3 d after the last house dust mite challenge. House dust mite-exposed mice treated with free PGE2 had fewer infiltrating eosinophils in lungs and lower YM1 serum levels than vehicle-treated mice. Macrophage-specific delivery of PGE2 did not affect lung inflammation. Adoptive transfer of PGE2-treated macrophages led to fewer infiltrating eosinophils, macrophages, (activated) CD4(+), and regulatory T lymphocytes in lungs. Our study shows that the redirection of macrophage polarization by using PGE2 inhibits development of allergic lung inflammation. This beneficial effect of macrophage repolarization is a novel avenue to explore for therapeutic purposes.


Assuntos
Asma/prevenção & controle , Dinoprostona/metabolismo , Eosinófilos/imunologia , Interleucina-10/metabolismo , Macrófagos/imunologia , Pneumonia/prevenção & controle , Pyroglyphidae/patogenicidade , Animais , Asma/etiologia , Asma/metabolismo , Células Cultivadas , Eosinófilos/citologia , Feminino , Interleucina-10/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/etiologia , Pneumonia/metabolismo
12.
Protein Expr Purif ; 121: 97-102, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26812600

RESUMO

Der p 2, a major allergen derived from the house dust mite Dermatophagoides pteronyssinus, is one of the most clinically relevant allergens worldwide. Recombinant Der p 2 (rDer p 2) is useful in clinical diagnosis and disease-specific immunotherapy. However, previous studies showed that Der p 2 can only be expressed in Escherichia coli (E. coli) cells as inclusion bodies, thus protein refolding is required to obtain functional products. Here we report a new method to produce biologically active Der p 2 protein in E. coli. N-terminal hexahistidine- and trigger factor (TF)-tagged Der p 2 was expressed in soluble form in E. coli and purified using a combination of chromatography processes. This procedure produced milligram-level high purity Der p 2 per liter of bacterial culture. Moreover, far-UV region circular dichroism (CD) analysis and serum specific IgE reactivity test demonstrated that the secondary structure and IgE reactivity properties of rDer p 2 produced in our study were almost identical to those of natural Der p 2 (nDer p 2). In conclusion, the method developed in this work provides a useful tool for the production of immunologically active recombinant Der p 2 for clinical applications.


Assuntos
Antígenos de Dermatophagoides/biossíntese , Proteínas de Artrópodes/biossíntese , Pyroglyphidae/imunologia , Proteínas Recombinantes/biossíntese , Animais , Antígenos de Dermatophagoides/genética , Antígenos de Dermatophagoides/imunologia , Antígenos de Dermatophagoides/isolamento & purificação , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/isolamento & purificação , Escherichia coli/genética , Expressão Gênica/imunologia , Humanos , Estrutura Secundária de Proteína , Pyroglyphidae/patogenicidade , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação
13.
Nutr. hosp ; 32(6): 2763-2770, dic. 2015. tab, graf
Artigo em Inglês | IBECS | ID: ibc-146142

RESUMO

Introduction: mites allergic asthma is caused by exposure to home dust mite (HDM). Der f 3 is believed to be one of the major allergens in mites allergic asthma. The work was to identify the immune characteristics of Der f 3 epitope-based vaccine containing T cell and B cell epitopes. Methods: T cell lines were generated from peripheral blood mononuclear cells of Der f 3 allergic patients. Three T cell epitopes and five B cell epitopes of Der f 3, which we identified previously, were selected to design a polypeptide (named Der f3-peptides). DNA constructions encoding these Der f 3-peptides were expressed in Escherichia coli. The T cell lines were stimulated with the peptides and tested for proliferative capacity and cytokine production. Results: plasmid pET28a (+)-Der f 3-peptides was constructed and expressed in E. coli BL21, and the Der f3-peptides protein was purified and confirmed by Western blotting. The Der f 3-peptides were recognized by the T cell clones from allergic patients. SI value of Der f 3 group and Der f 3-peptides group were both higher than that of PBS group (P< 0.05). Conclusions: our results demonstrate that several major T cell epitopes and B cell epitopes of Der f 3 can be valuable for designing the peptide-based immunotherapeutics for the mites allergic asthma (AU)


Introducción: el asma alérgica está causada por la exposición a los ácaros del polvo casero (HDM). Der f 3 se cree que es uno de los principales alérgenos en los ácaros del asma alérgica. El trabajo consistió en identificar las características inmunológicas de la vacuna basada en epítopo-Der f 3 que contienen las células T y las células B. Métodos: se generaron líneas de células T a partir de células mononucleares de sangre periférica de pacientes alérgicos a Der f 3. Tres epítopos de células T y cinco epítopos de células B de Der f 3, que hemos identificado previamente, fueron seleccionados para diseñar un polipéptido (denominados péptidos Der f 3). Construcciones de DNA que codifican estos péptidos Der f 3 se expresaron en Escherichia coli. Las líneas de células T se estimularon con los péptidos y se utilizaron en el ensayo por su capacidad proliferativa y la producción de citoquinas. Resultados: el plásmido pET28a (+) - Der f 3-péptidos se construyó y se expresaron en E. coli BL21, y la proteína de Der f 3-péptidos se purificó y se confirmaron mediante transferencia de Western. Los Der f 3-péptidos fueron reconocidos por los clones de células T procedentes de pacientes alérgicos. Valor SI de Der f 3 grupo y f grupo 3-péptidos Der eran tanto mayor que la del grupo de PBS (P <0,05). La capacidad de unión a IgE a Der f 3-péptidos (41, 25 ± 5, 67) μg/ml se redujo drásticamente en comparación con el de Der f 3 (83,60 ± 10,92) μg/ml (P <0,05). Conclusiones: nuestros resultados demuestran que varios de los principales epítopos de células T y de células B de Der f 3 pueden ser valiosos para el diseño de agentes inmunoterapéuticos basados en péptidos para los ácaros del asma alérgica (AU)


Assuntos
Humanos , Epitopos/uso terapêutico , Vacinas/farmacologia , Hipersensibilidade/prevenção & controle , Dessensibilização Imunológica/métodos , Pyroglyphidae/patogenicidade , Linfócitos T/imunologia , Citocinas/imunologia
14.
Allergol. immunopatol ; 43(4): 332-338, jul.-ago. 2015. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-139358

RESUMO

Background: Storage mites of the genus Acarus can be responsible for allergic sensitisation in domestic environments.Acarus gracilis is a frequent species in some geographical regions of the Iberian Peninsula. Since the allergenicity of this mite has not been described before, the objectives of this study were to characterise it immunologically, and to compare it with the closely related and more extensively studied speciesAcarus siro. Methods: Extracts from A. gracilis and A. siro cultures were characterised by Lowry, 1D and 2D-SDS and IEF. Zymogram, and determination of different enzymatic activities were performed. Skin prick solution of A. gracilis was tested in consecutive patients attending the Hospital of Mérida (Extremadura, Spain). Serum samples from eight individuals with positive skin prick test were collected. IgE determination, immunoblot and immunoblot-inhibition studies were performed. Results: Extracts of both species showed a very similar protein and allergenic profile. Allergens at 14 and 17 kDa were clearly recognised in both extracts by serum samples. Immunoblot-inhibition studies demonstrated that both extracts were totally inhibited by the opposite one. Enzymatic activity was similar in both cases with the most important differences being in kallikrein, serine protease and collagenase activities. Conclusion: The storage mite A. gracilis has a similar protein and allergen profile to A. siro and can induce allergic sensitisation. Due to the higher prevalence of this species respect to A. siro in some regions, more studies are needed to determine the clinical significance of sensitisation to this storage mite species (AU)


No disponible


Assuntos
Humanos , Pyroglyphidae/patogenicidade , Infestações por Ácaros/epidemiologia , Ácaros/patogenicidade , Hipersensibilidade Respiratória/imunologia , Apresentação Cruzada/imunologia , Immunoblotting/métodos , Cisteína Proteases/imunologia , Imunoglobulina E/imunologia , Ativação Enzimática/imunologia
15.
Biomed Res Int ; 2015: 421716, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064909

RESUMO

PURPOSE: To survey the species diversity of home dust mites (HDM) in Xishuangbanna, a tropical rainforest region in Southwest China. METHODS: From August 2010 to January 2011, mite-allergic patients and healthy controls were invited to participate. Dust samples from the patients' homes were collected, and mites in the samples were isolated. Permanent slides were prepared for morphologically based species determination. RESULTS: In total, 6316 mite specimens of morphologically identifiable species were found in 233 dust samples taken from 41 homes. The result shows that the mite family of Pyroglyphidae occupied the highest percentage of the total amount of mites collected, followed by Cheyletidae family. The most common adult Pyroglyphidae mites were Dermatophagoides (D.) farinae, D. pteronyssinus, and D. siboney. The most common mites found from other families were Blomia tropicalis, Tyrophagus putrescentiae, and Aleuroglyphus ovatus. Four main allergenic dust mite species D. farinae, D. pteronyssinus, D. siboney, and Blomia tropicalis were found to be coinhabiting in 6/41 homes. CONCLUSION: The HDM population in homes in Xishuangbanna, a tropical rainforest region in Southwest China, has its own characteristics. It has rich dust mite species and the dust mite densities do not show significant variation across seasons.


Assuntos
Alérgenos/isolamento & purificação , Asma/etiologia , Pyroglyphidae/genética , Alérgenos/genética , Animais , Asma/genética , Asma/fisiopatologia , China , Humanos , Pyroglyphidae/classificação , Pyroglyphidae/patogenicidade , Floresta Úmida , Estações do Ano , Especificidade da Espécie
16.
Angiogenesis ; 18(1): 1-11, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25149641

RESUMO

Expanded and aberrant bronchial vascularity, a prominent feature of the chronic asthmatic airway, might explain persistent airway wall edema and sustained leukocyte recruitment. Since it is well established that there are causal relationships between exposure to house dust mite (HDM) and the development of asthma, determining the effects of HDM in rats, mammals with a bronchial vasculature similar to humans, provides an opportunity to study the effects of bronchial angiogenesis on airway function directly. We studied rats exposed bi-weekly to HDM (Der p 1; 50 µg/challenge by intranasal aspiration, 1, 2, 3 weeks) and measured the time course of appearance of increased blood vessels within the airway wall. Results demonstrated that within 3 weeks of HDM exposure, the number of vessels counted within airway walls of bronchial airways (0.5-3 mm perimeter) increased significantly. These vascular changes were accompanied by increased airway responsiveness to methacholine. A shorter exposure regimen (2 weeks of bi-weekly exposure) was insufficient to cause a significant increase in functional vessels or reactivity. Yet, 19F/1H MR imaging at 3T following αvß3-targeted perfluorocarbon nanoparticle infusion revealed a significant increase in 19F signal in rat airways after 2 weeks of bi-weekly HDM, suggesting earlier activation of the process of neovascularization. Although many antigen-induced mouse models exist, mice lack a bronchial vasculature and consequently lack the requisite human parallels to study bronchial edema. Overall, our results provide an important new model to study the impact of bronchial angiogenesis on chronic inflammation and airways hyperreactivity.


Assuntos
Asma/fisiopatologia , Hiper-Reatividade Brônquica/fisiopatologia , Modelos Animais de Doenças , Neovascularização Patológica/parasitologia , Pyroglyphidae/patogenicidade , Resistência das Vias Respiratórias/fisiologia , Análise de Variância , Animais , Artérias Brônquicas/patologia , Hiper-Reatividade Brônquica/parasitologia , Primers do DNA/genética , Fluorcarbonetos , Pulmão/patologia , Imagem por Ressonância Magnética , Cloreto de Metacolina , Nanopartículas , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Elastômeros de Silicone , Fatores de Tempo
18.
Allergol. immunopatol ; 42(3): 216-223, mayo-jun. 2014. tab, graf
Artigo em Inglês | IBECS | ID: ibc-122681

RESUMO

Background: Conventional immunotherapy for allergy with 3–5 years of treatment period has poor compliance. Ultra-rush sublingual immunotherapy with a shorter period of treatment can have better compliance. There are very few studies on ultra-rush sublingual immunotherapy all over the world. Objectives: (1) To determine allergen sensitivity among allergic rhinitis patients. (2) To assess safety, tolerability and clinical efficacy of ultra-rush sublingual immunotherapy. Methods: The present study was conducted in Allergy clinic, KIMS Hospital & Research Centre, Bangalore, India from January 2010 to June 2011. After obtaining Institutional Ethics Committee approval, 40 allergic rhinitis patients (according to ARIA guidelines) in the 18–60 years age group who were positive for aeroallergens in skin prick test were recruited for ultra-rush sublingual immunotherapy (20 min initial phase and 4-month maintenance phase) and followed for 8 months with symptom and treatment diary. Results: Out of 40 patients, the majority, 36 (90.00%) patients were sensitive to house dust mites. Six patients had seven immediate adverse reactions and seven patients had eight delayed adverse reactions. All subsided without medication or with symptomatic oral medications. All patients tolerated ultra-rush SLIT and there was significant decrease in both symptom-score and treatment received in these patients. Conclusion: Ultra-rush SLIT regimen has excellent safety, tolerability and clinical efficacy among allergic rhinitis patients (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Dessensibilização Imunológica/métodos , Administração Sublingual , Rinite Alérgica Perene/terapia , Segurança do Paciente , Pyroglyphidae/patogenicidade , Alérgenos/uso terapêutico
19.
Allergol. immunopatol ; 42(2): 120-126, mar.-abr. 2014. tab, graf
Artigo em Inglês | IBECS | ID: ibc-121010

RESUMO

Purpose: Rhinitis and rhinosinusitis are major concerns in public health. Mites are important aetiological agents in the tropics. The present study investigated the in vivo response to mite allergens in patients with rhinitis and rhinosinusitis. Methods: All patients with presumptive nasal allergy were included. Skin tests were done with inhalants and mite extracts. Patients were classified as allergic or non-allergic according to skin tests and history. Results: Out of 229 patients, 175 (76.4%) showed positive skin tests. Allergic patients showed positivity to mites in 97.1% of cases, 51.4% to dog dander; 40.5% to cat dander; 36.5% to German cockroach; 22.8% to moulds; and 21.1% to grass pollens. Dermatophagoides farinae induced responses in 90.8% of patients, D. pteronyssinus in 90.1%, Blomia tropicalis in 74.8%, Glycyphagus domesticus in 62.2%, Chortoglyphus arcuatus in 58.2%, Acarus siro in 46.2%, Lepidoglyphus destructor in 35.4%, and Tyrophagus putrescentiae in 35.0%. Higher correlations were found between skin test diameters induced by mites from the same family. Conclusions: Sensitisation to inhalant allergens is present in 76% of allergy clinics’ patients with rhinitis or rhinosinusitis. Our results confirm previous observations showing that mites constitute the most important cause of respiratory allergy in tropical settings and suggest that mite allergen cross-reactivity is responsible for the positivity of skin tests to mites not present in the patient's environment since the species Glycyphagus, Chortoglyphus, Acarus, Lepidoglyphus and Tyrophagus have not been found in Caracas house dust (AU)


No disponible


Assuntos
Humanos , Ácaros/patogenicidade , Hipersensibilidade Respiratória/epidemiologia , Clima Tropical , Dermatophagoides pteronyssinus/patogenicidade , Pyroglyphidae/patogenicidade , Doença Ambiental/epidemiologia , Dermatophagoides farinae/patogenicidade
20.
Allergol. immunopatol ; 42(1): 50-55, ene.-feb. 2014. tab, graf
Artigo em Inglês | IBECS | ID: ibc-119053

RESUMO

Background: Allergic rhinitis and asthma due to mite sensitisation are diseases which are frequently associated and characterised by persistent inflammation. In the present study, we aimed to investigate the relationship between nasal airflows and nasal eosinophils in patients with asthma and/or rhinitis due to house dust mite sensitisation. Methods: Twenty-four children with both rhinitis and asthma (R + A), 13 children with rhinitis and no asthma (R) and 10 non-allergic healthy children were evaluated prospectively. The patients belonging to the first two groups had moderate–severe grade of nasal obstruction. Total nasal symptom scores, peak nasal inspiratory flows (PNIFs) obtained by anterior rhinomanometry, skin prick tests, nasal eosinophils and FEV1 values were all assessed. Results: Percentages of nasal eosinophils and PNIFs in patients with R + A and R (r = −0.415, p = 0.04) were found to be statistically significant and to have an inverse correlation. Skin prick tests were also significantly correlated with nasal eosinophils and PNIFs (r = 0.372, p = 0.01 and r = −0.306, p = 0.04, respectively). Both PNIFs and nasal eosinophils of patients with R + A were significantly correlated with FEV1 values (r = −0.641, p = 0.001 and r = 0.548, p = 0.007, respectively). Conclusion: In this study, a close relationship was demonstrated between eosinophil infiltration and nasal airflows in children having asthma and/or rhinitis monosensitised to mites. Additionally, the significant association found between FEV1 values and nasal eosinophils or PNIFs supported the close link of upper and lower airways (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Criança , Eosinófilos/imunologia , Asma/imunologia , Rinite Alérgica Perene/imunologia , Hipersensibilidade Respiratória/imunologia , Pyroglyphidae/patogenicidade , Doença Ambiental , Poluição do Ar em Ambientes Fechados/análise
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