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1.
Int J Mol Sci ; 20(19)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581442

RESUMO

Garlic (Allium sativum L.) has been used extensively as a food ingredient and medicinally, but the effect on asthmatic airway inflammation has not been studied in detail. We accordingly explored the protective effects exerted by various garlic fraction extracts against airway inflammation with Dermatophagoides pteronyssinus (Der p)-induced allergic asthma in vivo and in vitro. Garlic extraction was realized using n-hexane, dichloromethane, ethylacetate, n-butanol, and water in sequence to obtain different fraction extracts. Mice were orally administered different fractions (80 mg/kg) daily for four weeks. The histological results showed that the water fraction could ameliorate lung-based goblet cell hyperplasia, inflammatory cell infiltration, and mucus hypersecretion. The water fraction extracts decreased IgE and IgG1, and they decreased inflammatory cells as quantified in bronchoalveolar lavage fluid (BALF); however, they increased IgG2a in serum. Moreover, the water fraction extracts increased IFN-γ and IL-12 (both constituting Th1 cytokines) in BALF, but they reduced IL-13, -4, and -5 (all constituting Th2 cytokines), and also inhibited the expression of IL-1ß, IL-6, and TNF-α. The water fraction also inhibited the PI3K/Akt/NF-κB signal pathways in A549 cells. These findings suggest that water fraction extracts of garlic have a clear anti-inflammatory effect on Der p-induced allergic asthma.


Assuntos
Antiasmáticos/farmacologia , Antígenos de Dermatophagoides/imunologia , Alho/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Hipersensibilidade Respiratória/imunologia , Animais , Antiasmáticos/química , Antiasmáticos/isolamento & purificação , Líquido da Lavagem Broncoalveolar , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Modelos Animais de Doenças , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Mediadores da Inflamação/metabolismo , Contagem de Leucócitos , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/metabolismo , Transdução de Sinais
2.
Iran J Allergy Asthma Immunol ; 18(4): 369-378, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31522445

RESUMO

Interleukin (IL)-4-producing-CD8 (cytotoxic T cells, Tc) contribute to lung eosinophilia and airway hyper-responsiveness (AHR) to an antigen. CD4+CD25+ regulatory T cells (Tregs) attenuate airway inflammation and AHR. This study investigated whether Tregs decrease Tc2frequencies in ovalbumin (OVA)-induced asthma model of mice. Female C57BL/6 mice were sensitized with OVA intraperitoneally and challenged with OVA intranasally to induce allergic asthma model. Tregs were sorted by fluorescence activated cell sorting (FACS) and magnetic activated cell sorting (MACS) microbeads. OVA-sensitized mice were injected with Tregs or phosphate buffer saline (PBS) by tail vein ahead of the first challenge. Airway inflammation and airway hyper-responsiveness (AHR)were evaluated by histological analysis and invasive method, respectively. OVA-specific IgE and cytokine levels were detected by ELISA. Flow cytometry was used to detect the percentages of Tc1 and Tc2. Gata3 and T-bet mRNA was determined by quantitative PCR (qPCR). OVA-sensitized and challenged mice displayed typical asthma features, which included eosinophilic airway inflammation, higher levels of Th2 cytokines and AHR. Gata3 mRNA, Tc2 frequencies and OVA-specific IgE levels were significantly increased in OVA-sensitized and challenged mice. Compared to PBS treatment, Tregs decreased Tc2 frequencies, airway inflammation, Th2 cytokine levels and AHR in OVA-sensitized and challenged mice. IL-13 levels were negatively correlated with Tc1 frequencies and with IFNg levels in experimental mice. Our results demonstrated that Tregs could prevent airway inflammation and AHR by decreasing Tc2 frequencies and cytokine levels in OVA-induced asthma model of mice, supporting Tregmight be as a potent therapeutic target for alleviating airway inflammation and AHR.


Assuntos
Asma/imunologia , Linfócitos T CD8-Positivos/imunologia , Comunicação Celular/imunologia , Linfócitos T Reguladores/imunologia , Alérgenos/imunologia , Animais , Asma/metabolismo , Biomarcadores , Antígenos CD4/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-4/metabolismo , Contagem de Linfócitos , Camundongos , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo
3.
Int Arch Allergy Immunol ; 180(3): 173-181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31537004

RESUMO

Allergic diseases affect more than 25% of the global population. Der p 2 is the major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus. Allergen-specific immunotherapy is the only treatment to change the course of allergic diseases. In this study, two synthesized Der p 2 peptides coupled to cross-reacting material 197 (CRM197) showed reduced IgE reactivity and allergenic activity. CRM197-coupled Der p 2 peptides induced rDer p 2-specific IgG1 antibodies in mice, which could inhibit HDM-allergic patients' IgE binding to rDer p 2. The immunity effects of CRM197-coupled Der p 2 peptides were studied in an rDer p 2-induced asthma mouse model. CRM197-coupled Der p 2 peptides can suppress asthmatic airway inflammation in this model. Analysis of IL-4, IL-5, and IFN-γ levels in bronchoalveolar lavage fluid revealed that the suppression was associated with a shift from a Th2 to a Th1 response. Thus, CRM197-bound Der p 2 peptides exhibited less allergenic activity than the rDer p 2 allergen, which preserved immunogenicity and may be candidates for mite allergy vaccines.


Assuntos
Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Asma/terapia , Proteínas de Bactérias/imunologia , Inflamação/terapia , Pulmão/imunologia , Peptídeos/imunologia , Hipersensibilidade Respiratória/terapia , Animais , Antígenos de Dermatophagoides/química , Proteínas de Artrópodes/química , Asma/imunologia , Proteínas de Bactérias/química , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Inflamação/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/química , Hipersensibilidade Respiratória/imunologia , Equilíbrio Th1-Th2 , Vacinas/imunologia
4.
Int Arch Allergy Immunol ; 180(1): 1-9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242493

RESUMO

BACKGROUND: An inverse relation between Helicobacter pylori infection and asthma has been shown in epidemiological studies. Infection with H. pylori, or application of an extract of it before or after sensitization, inhibits allergic airway disease in mice. OBJECTIVES: The aim of this study was to investigate the effect of an extract of H. pylori on allergic airway disease induced by repeated allergen exposure in mice that were sensitized and challenged prior to extract application. METHOD: C57BL/6 mice were intranasally (i.n.) sensitized and challenged with house dust mite (HDM). After a minimum of 4 weeks, mice received the H. pylori extract intraperitoneally and were rechallenged i.n. with HDM. Allergen-specific antibodies were measured by ELISA. Cells present in the bronchoalveolar lavage fluid and dendritic cell (DC) subsets in the lung tissue were analyzed by flow cytometry. Tissue inflammation and goblet cell hyperplasia were assessed by histology. Cells of the mediastinal lymph node (mLN) were isolated and in vitro restimulated with HDM or H. pylori extract. RESULTS: Treatment with H. pylori extract before rechallenge reduced allergen-specific IgE, the DC numbers in the tissue, and goblet cell hyperplasia. Cells isolated from mLN of mice treated with the extract produced significantly more IL-10 and IL-17 after in vitro restimulation with HDM. mLN cells of H. pylori-treated mice that were re-exposed to the H. pylori extract produced significantly more interferon gamma. CONCLUSIONS: An extract of H. pylori is effective in reducing mucus production and various features of inflammation in HDM rechallenged mice.


Assuntos
Alérgenos/imunologia , Antígenos de Bactérias/imunologia , Células Caliciformes/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/patologia , Animais , Biomarcadores , Biópsia , Citocinas/metabolismo , Exposição Ambiental , Feminino , Infecções por Helicobacter/microbiologia , Hiperplasia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Imunofenotipagem , Camundongos , Pyroglyphidae/imunologia
5.
Immunity ; 51(1): 169-184.e5, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31231035

RESUMO

Naive CD4+ T cells differentiate into functionally diverse T helper (Th) cell subsets. Th2 cells play a pathogenic role in asthma, yet a clear picture of their transcriptional profile is lacking. We performed single-cell RNA sequencing (scRNA-seq) of T helper cells from lymph node, lung, and airways in the house dust mite (HDM) model of allergic airway disease. scRNA-seq resolved transcriptional profiles of naive CD4+ T, Th1, Th2, regulatory T (Treg) cells, and a CD4+ T cell population responsive to type I interferons. Th2 cells in the airways were enriched for transcription of many genes, including Cd200r1, Il6, Plac8, and Igfbp7, and their mRNA profile was supported by analysis of chromatin accessibility and flow cytometry. Pathways associated with lipid metabolism were enriched in Th2 cells, and experiments with inhibitors of key metabolic pathways supported roles for glucose and lipid metabolism. These findings provide insight into the differentiation of pathogenic Th2 cells in the context of allergy.


Assuntos
Asma/imunologia , Hipersensibilidade Respiratória/imunologia , Sistema Respiratório/imunologia , Subpopulações de Linfócitos T/imunologia , Células Th2/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Modelos Animais de Doenças , Humanos , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Orexina/genética , Pyroglyphidae/imunologia , Análise de Sequência de RNA , Análise de Célula Única , Transcriptoma
6.
J Biosci ; 44(2)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31180054

RESUMO

This study was conducted to determine whether exposure to particulate matter 2.5 (PM2.5) affects the immune tolerance of neonatal mice via the regulation of PD-L1 expression. One-week-old BALB/c mice were exposed to PM2.5 for 8 days. From day 8 to day 18, the mice were treated with 5 µg house dust mite (HDM) (i. n.) every two days. Adenovirus-carried PD-L1 overexpression vectors were infected into mice via nasal inhalation 6 days after exposure to PM2.5. Airway hyperresponsiveness (AHR) was examined in mice 19 days after exposure to PM2.5, and the related parameters of airway inflammation were studied on day 22. Co-exposure to PM2.5 and HDM reduced PD-L1 expression but greatly increased infiltration of inflammatory cells, which was reversed by PD-L1 overexpression. Co-exposure to PM2.5 and HDM also elevated serum IL-4, IL-5 and IL-13 levels and reduced TGF-ß level. Exposure to PM2.5 alone slightly increased the numbers of dendritic cells (DCs) but reduced the numbers of antigen-presenting cells expressing PD-L1 and Treg cells. Therefore, early exposure to PM2.5 reduced PD-L1 expression in the lungs of neonatal mice, which interfered with immune tolerance establishment and subsequently resulted in allergic airway inflammation.


Assuntos
Antígeno B7-H1/imunologia , Células Dendríticas/efeitos dos fármacos , Tolerância Imunológica/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Material Particulado/administração & dosagem , Hipersensibilidade Respiratória/imunologia , Adenoviridae/genética , Adenoviridae/imunologia , Administração por Inalação , Animais , Animais Recém-Nascidos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Células Dendríticas/imunologia , Células Dendríticas/patologia , Regulação da Expressão Gênica , Vetores Genéticos/administração & dosagem , Vetores Genéticos/química , Vetores Genéticos/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Pyroglyphidae/química , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/genética , Hipersensibilidade Respiratória/patologia , Transdução de Sinais , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologia
7.
BMC Immunol ; 20(1): 18, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164097

RESUMO

BACKGROUND: Mouse models have been extremely valuable in identifying the fundamental mechanisms of airway inflammation that underlie human allergic asthma. Several models are commonly used, employing different methods and routes of sensitisation, and allergens of varying clinical relevance. Although all models elicit similar hallmarks of allergic airway inflammation, including airway eosinophilia, goblet cell hyperplasia and cellular infiltration in lung, it is not established whether they do so by involving the same mechanisms. RESULTS: We compared the impact of inactivation of various innate or adaptive immune genes, as well as sex, in different models of allergic airway inflammation in mice of C57BL/6 background. Chicken ovalbumin (OVA) and house dust mite (HDM) were used as allergens in settings of single or multiple intranasal (i.n.) challenges, after sensitisation in adjuvant or in adjuvant-free conditions. Eosinophil numbers in the broncho-alveolar lavage and lung histopathology were assessed in each model. We found that Major Histocompatibility Complex Class II (MHCII) deficiency and lack of conventional CD4+ T cells had the most profound effect, essentially ablating airway eosinophilia and goblet cell hyperplasia in all models. In contrast, Thymic stromal lymphopoietin receptor (TSLPR) deficiency greatly reduced eosinophilia but had a variable effect on goblet cells. CD1d deficiency and lack of Natural Killer T (NKT) cells moderately impaired inflammation in OVA models but not HDM, whereas sex affected the response to HDM but not OVA. Lastly, defective Toll-like receptor (TLR)4 expression had only a relatively modest overall impact on inflammation. CONCLUSION: All the models studied were comparably dependent on adaptive CD4+ T cell responses and TSLP. In contrast, sex, NKT cells and TLR4 appeared to play subtler and more variable roles that were dependent on the type of allergen and mode of immunization and challenge. These results are consistent with clinical data suggesting a key role of CD4+ T cells and TSLP in patients with allergic asthma.


Assuntos
Alérgenos/imunologia , Eosinofilia/imunologia , Células Caliciformes/patologia , Pulmão/imunologia , Hipersensibilidade Respiratória/imunologia , Imunidade Adaptativa/genética , Adjuvantes Imunológicos , Animais , Antígenos de Dermatophagoides/imunologia , Feminino , Humanos , Imunidade Inata/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Ovalbumina/imunologia
8.
Int Immunopharmacol ; 73: 435-441, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154288

RESUMO

Studies suggest that hydrogen sulfide (H2S) plays a relevant and beneficial role in the pathophysiology of pulmonary allergic diseases, such as asthma. These diseases may be triggered by changes in airway epithelium caused by repeated exposure to environmental allergens. This study aimed to investigate whether H2S protects against bronchial epithelium apoptosis in allergic inflammation in mice. The effects of H2S on the production of Th2 cytokines and on the infiltration of pulmonary inflammatory cells were also studied. Female BALB/c mice previously sensitized with ovalbumin (OVA) were treated with H2S donor (sodium hydrosulfide [NaHS]) 30 min prior to OVA challenge. After euthanasia (48 h post challenge), the right lung was homogenized to study apoptosis protein expression and to analyze cytokine levels in lung tissue. The left lobe was fixed in formalin for morphological analysis of lung tissue and verification of apoptosis in situ by the TUNEL assay. Histological results showed that NaHS reduced the airway inflammatory infiltrate and prevented an increase in the IL-4, IL-5 and IL-25 levels caused by OVA challenge. Activation of caspase 3 and FasL in response to the allergen was also fully prevented by NaHS treatment. TUNEL staining showed that the challenge from OVA significantly increased the rate of apoptosis in the bronchiolar epithelium, and that this incremental apoptosis was abolished by NaHS treatment. In conclusion, our results showed that H2S donor has a protective effect against airway epithelium damage caused by an allergic reaction, and represents a potential agent in treating allergic lung disorders, such as asthma.


Assuntos
Citocinas/imunologia , Epitélio/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Hipersensibilidade Respiratória/imunologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Epitélio/imunologia , Epitélio/patologia , Feminino , Sulfeto de Hidrogênio , Pulmão/imunologia , Pulmão/patologia , Camundongos Endogâmicos BALB C , Ovalbumina , Hipersensibilidade Respiratória/patologia , Sulfetos/farmacologia
9.
Ann Allergy Asthma Immunol ; 123(3): 263-270, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152786

RESUMO

BACKGROUND: CD163 is one of the scavenger receptors that are specifically expressed on macrophages and are well known to be upregulated by various inflammatory responses, including chronic obstructive pulmonary disease in airway diseases. OBJECTIVE: To evaluate the CD163 expression in the lungs of patients with fatal asthma and investigated whether CD163 contributes to the pathogenesis in asthma. METHODS: The CD163 expressions in the lungs of patients with fatal asthma (n = 9) and in those of nonasthma control subjects (n = 8) were tested by immunohistochemistry. In mouse models of asthma, airway hyperresponsiveness (AHR) and the numbers of airway inflammatory cells in the bronchoalveolar lavage fluid (BALF) were analyzed in the CD163-deficient mice and the control wild-type mice. RESULTS: The numbers of CD163-positive macrophages in the lung tissues were significantly increased in the all 6 patients with fatal asthma than in the control subjects. In mouse models of asthma, AHR and the numbers of infiltrating leukocytes, such as eosinophils, lymphocytes, neutrophils, and macrophages, in the BALF were significantly decreased in the CD163-deficient mice when compared with control wild-type mice. The concentrations of interferon γ and interleukin 5 in the BALF were significantly decreased in the CD163-deficient mice when compared with those in the control wild-type mice. CONCLUSION: CD163 may play important roles in airway inflammation and AHR in asthma.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Asma/imunologia , Pulmão/patologia , Macrófagos/imunologia , Receptores de Superfície Celular/metabolismo , Hipersensibilidade Respiratória/imunologia , Idoso , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Asma/diagnóstico , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Contagem de Leucócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Pessoa de Meia-Idade , Receptores de Superfície Celular/genética , Hipersensibilidade Respiratória/diagnóstico
10.
Artigo em Inglês | MEDLINE | ID: mdl-31181728

RESUMO

Background: Physical exercise is often recommended as additional treatment for people suffering from allergic rhinitis and/or asthma, but less is known about the specific effects of recreational winter outdoor exercise on allergic airway inflammation. Methods: We performed a longitudinal, randomized controlled intervention study to investigate the effects of recreational winter exercise on allergic airway inflammation, quality of life, spirometry and cardiorespiratory fitness in adults suffering from allergic rhinitis and/or asthma. The exercise group participated in a ten-day winter sports program. The control group did not receive any intervention. Results: A significant improvement of fractional oral exhaled nitric oxide (FeNO; p = 0.008, day 10) and a significant decrease in FeNO after a single 4 h hiking tour (p < 0.001, time effect) were observed for the exercise group. The nasal eosinophilic cell count revealed a short-term reduction (p = 0.021, treatment effect) in the exercise group and for the visual analogue scale sustainable improvements in allergic symptoms (p < 0.001, day 60) were found. No adverse effects of outdoor winter exercise were observed. Conclusion: Recreational winter exercise at moderately cold temperatures reduces allergic airway inflammation measured as FeNO, nasal eosinophilic cell count and induces sustainable improvements in allergic symptoms.


Assuntos
Terapia por Exercício , Hipersensibilidade Respiratória/terapia , Adulto , Eosinófilos/imunologia , Exercício , Expiração , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/imunologia , Óxido Nítrico/metabolismo , Qualidade de Vida , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/fisiopatologia , Estações do Ano , Espirometria , Escala Visual Analógica , Adulto Jovem
12.
Rev Mal Respir ; 36(4): 442-446, 2019 Apr.
Artigo em Francês | MEDLINE | ID: mdl-31006580

RESUMO

Severe asthma required high dose of corticosteroids combined with biotherapies to control more or less asthma symptoms and lead to the decrease of patients' quality of life on long term. Recent studies show that hypoallergenic peptides derived from allergen can prevent airway hyperresponsiveness, decrease Th2 response and also allergen-specific IgE in mouse models of allergic asthma. Even if some peptides mechanisms remain unknown, their fast efficacy with low doses of allergens make peptide immunotherapy a new promising approach in allergic asthma.


Assuntos
Alérgenos/química , Asma/terapia , Dessensibilização Imunológica/métodos , Peptídeos/uso terapêutico , Alérgenos/imunologia , Alérgenos/uso terapêutico , Animais , Asma/imunologia , Humanos , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/uso terapêutico , Peptídeos/imunologia , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/terapia
13.
Int Arch Allergy Immunol ; 179(3): 192-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30999298

RESUMO

AIM: Asthma appears to be a common comorbid condition in children with sickle cell disease (SCD), and such individuals may be at a higher risk for increased morbidity and mortality. However, several reports have indicated that asthma severity is not particularly high in those with SCD, and airway hyperreactivity and wheeze may be independently associated with SCD. In SCD mice, exacerbated allergic airway disease (AAD) has been observed in response to the model antigen ovalbumin (OVA). We sought to determine if allergic lung inflammation is also exacerbated in SCD mice when they are exposed to the human allergen, house dust mite (HDM). METHODS AND RESULTS: Eosinophil counts in bronchoalveolar lavage fluid were determined by cytocentrifugation and increased in both wild-type (WT) and SCD mice after acute exposure to a high dose (25 µg) of HDM, which then decreased in chronically exposed mice. WT mice exposed to a low dose of HDM (1 µg) followed the same pattern of eosinophil flux, but SCD mice did not induce much eosinophilia after acute exposure to HDM. As was observed in previous studies, lung lesions similarly increased in severity in both WT and SCD mice after acute exposure to HDM, which remained elevated after chronic exposure. Furthermore, serum HDM-specific IgE titers similarly increased and selected serum cytokines were similar in both WT and SCD mice. CONCLUSION: These results contrast with previous reports of exacerbated AAD in SCD mice exposed to OVA and support the alternative hypothesis that asthmatic responses are normal in those with SCD.


Assuntos
Alérgenos/imunologia , Anemia Falciforme/imunologia , Ovalbumina/imunologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/imunologia , Anemia Falciforme/sangue , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/sangue , Feminino , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Camundongos Transgênicos , Hipersensibilidade Respiratória/sangue
14.
JAMA Pediatr ; 173(6): 544-552, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30933255

RESUMO

Importance: Rhinovirus infection in early life, particularly with allergic sensitization, is associated with higher risks of developing recurrent wheeze and asthma. While emerging evidence links different rhinovirus species (eg, rhinovirus C) to a higher severity of infection and asthma exacerbation, to our knowledge, little is known about longitudinal associations of rhinovirus C infection during infancy with subsequent morbidities. Objective: To examine the association of different viruses (respiratory syncytial virus [RSV], rhinovirus species) in bronchiolitis with risks of developing recurrent wheeze. Design, Setting, and Participants: This multicenter prospective cohort study of infants younger than 1 year who were hospitalized for bronchiolitis was conducted at 17 hospitals across 14 US states during 3 consecutive fall to winter seasons (2011-2014). Exposures: Major causative viruses of bronchiolitis, including RSV (reference group) and 3 rhinovirus species (rhinovirus A, B, and C). Main Outcomes and Measures: Development of recurrent wheeze (as defined in national asthma guidelines) by age 3 years. Results: This analytic cohort comprised 716 infants who were hospitalized for RSV-only or rhinovirus bronchiolitis. The median age was 2.9 months (interquartile range, 1.6-3.8 months), 541 (76%) had bronchiolitis with RSV only, 85 (12%) had rhinovirus A, 12 (2%) had rhinovirus B, and 78 (11%) had rhinovirus C infection. Overall, 231 (32%) developed recurrent wheeze by age 3 years. In the multivariable Cox model, compared with infants with RSV-only infection, the risk of recurrent wheeze was not significantly different in those with rhinovirus A or B (rhinovirus A: hazard ratio [HR], 1.27; 95% CI, 0.86-1.88; rhinovirus B: HR, 1.39; 95% CI, 0.51-3.77; both P > .10). By contrast, infants with rhinovirus C had a significantly higher risk (HR, 1.58; 95% CI, 1.08-2.32). There was a significant interaction between virus groups and IgE sensitization on the risk of recurrent wheeze (P for interaction < .01). Only infants with both rhinovirus C infection and IgE sensitization (to food or aeroallergens) during infancy had significantly higher risks of recurrent wheeze (HR, 3.03; 95% CI, 1.20-7.61). Furthermore, compared with RSV-only, rhinovirus C infection with IgE sensitization was associated with significantly higher risks of recurrent wheeze with subsequent development of asthma at age 4 years (HR, 4.06; 95% CI, 1.17-14.1). Conclusions and Relevance: This multicenter cohort study of infants hospitalized for bronchiolitis demonstrated between-virus differences in the risk of developing recurrent wheeze. Infants with rhinovirus C infection, along with IgE sensitization, had the highest risk. This finding was driven by the association with a subtype of recurrent wheeze: children with subsequent development of asthma.


Assuntos
Bronquiolite Viral/complicações , Infecções por Coxsackievirus/complicações , Enterovirus/imunologia , Hipersensibilidade Alimentar/complicações , Imunoglobulina E/sangue , Hipersensibilidade Respiratória/complicações , Sons Respiratórios/etiologia , Asma/etiologia , Biomarcadores/sangue , Bronquiolite Viral/imunologia , Pré-Escolar , Infecções por Coxsackievirus/imunologia , Feminino , Seguimentos , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Humanos , Lactente , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Hipersensibilidade Respiratória/sangue , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/imunologia , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/imunologia , Fatores de Risco
15.
Int Arch Allergy Immunol ; 179(3): 187-191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943491

RESUMO

BACKGROUND: The prevalence of peanut allergy (PA) is constantly on the rise. Atopic dermatitis (AD) is a major risk factor for developing food allergy. Some bath oils and skin creams used for treating AD contain peanut oil, and it has been suggested that exposure to peanut allergens through a disrupted skin barrier is a potential cause of PA. Our aim was to investigate whether application of peanut oil to irritated skin causes a systemic or respiratory allergic response to peanuts in an animal model. METHODS: BALB/c mice underwent epicutaneous sensitization with either peanut oil (PM, n = 9) or phosphate buffered solution (controls, n = 9) daily for 5 consecutive days. Ten days after the last exposure the mice were challenged with intranasal peanut protein for 5 consecutive days. Bronchial alveolar lavage fluid was collected for cellular studies and measurement of cytokine levels. Sera were collected for immunoglobulin E (IgE) measurement. RESULTS: Epicutaneous peanut oil sensitization increased leukocyte and eosinophil counts and interleukin-13 levels (p = 0.003, p = 0.0006 and p = 0.03, respectively), in addition to increasing total serum IgE (p = 0.03). CONCLUSIONS: The results suggest that topical application of peanut oil may play a role in the etiology of PA.


Assuntos
Alérgenos/administração & dosagem , Antígenos de Plantas/administração & dosagem , Hipersensibilidade a Amendoim , Óleo de Amendoim/administração & dosagem , Hipersensibilidade Respiratória , Administração Cutânea , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Feminino , Imunoglobulina E/sangue , Interleucina-13/imunologia , Interleucina-4/imunologia , Contagem de Leucócitos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos Endogâmicos BALB C , Hipersensibilidade a Amendoim/sangue , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade Respiratória/sangue , Hipersensibilidade Respiratória/imunologia
16.
BMB Rep ; 52(4): 283-288, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30885291

RESUMO

Foxp3+ regulatory CD4+ T (Treg) cells play an essential role in preventing overt immune responses against self and innocuous foreign antigens. Selective expansion of endogenous Treg cells in response to the administration of interleukin (IL)-2/antibody complex, such as the IL-2/JES6-1 complex (IL-2C) in mice, is considered an attractive therapeutic approach to various immune disorders. Here, we investigated the therapeutic potential of IL-2C in allergic airway inflammation models. IL-2C treatment ameliorated Th17-mediated airway inflammation; however, unexpectedly, IL-2C treatment exacerbated Th2-mediated allergic airway inflammation by inducing the selective expansion of Th2 cells and type-2 innate lymphoid cells. We also found that IL-2 signaling is required for the expansion of Th2 cells in lymphoproliferative disease caused by Treg cell depletion. Our data suggest that IL-2C is selectively applicable to the treatment of allergic airway diseases depending on the characteristics of airway inflammation. [BMB Reports 2019; 52(4): 283-288].


Assuntos
Fatores de Transcrição Forkhead/imunologia , Interleucina-2/imunologia , Interleucina-2/farmacologia , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/terapia , Células Th2/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Asma/imunologia , Asma/terapia , Citocinas/imunologia , Hipersensibilidade/imunologia , Tolerância Imunológica/imunologia , Imunidade Inata/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Th17/imunologia
17.
Immunobiology ; 224(3): 462-469, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30795860

RESUMO

Peptide immunotherapy (PIT) represents a safe and efficacious therapeutic modality for allergic diseases. Present study evaluates immunotherapeutic potential of T cell peptides of major cockroach allergen, Per a 10 in murine model of airway allergy. Treatment with peptides T-P8 and T-P10 demonstrated maximal resolution of pathophysiological features such as reduced recruitment of inflammatory cells to airways, lowered specific IgE, induction of IgG2a antibodies in serum, immune deviation towards Th1 cytokine milieu, suppression of Th2 cytokines in BALF and splenocyte culture supernatant and resolution of lung inflammation. A significant increase in CD4+Foxp3+ cells in spleen indicate towards induction of T regulatory cell mediated peripheral tolerance characterized by shift in cytokine milieu from Th2 to T regulatory cytokines. PIT modulates regulation of immune responses at both local and systemic levels, contributes towards holistic improvement in allergic features in mice and thus demonstrate potential for safe, specific and efficacious treatment for cockroach allergy.


Assuntos
Asma/imunologia , Imunoterapia/métodos , Hipersensibilidade Respiratória/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Alérgenos/imunologia , Animais , Asma/terapia , Modelos Animais de Doenças , Epitopos de Linfócito T/imunologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunidade Celular , Imunoglobulina E/metabolismo , Imunomodulação , Proteínas de Insetos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Hipersensibilidade Respiratória/terapia , Vacinas de Subunidades
18.
J Vet Med Sci ; 81(4): 541-544, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30773519

RESUMO

The aim of this study is to identify the combined effect of multiple chemicals to the development of allergy. In this study, the effect of prenatal exposure to an organochlorine agent methoxychlor (MXC) and/or an organophosphate agent parathion (PARA) on trimellitic anhydride-induced allergic airway inflammation was examined in mice. Eosinophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly enhanced by MXC + PARA exposure compared to that of the control, MXC, and PARA groups. In the hilar lymph node, only slight increases in B-cell infiltration, as well as IL-6 and IL-9 secretions were observed in MXC + PARA group, and no effect was observed in the individual treatment groups. Our findings imply that prenatal exposure to some combinations of multiple chemicals may exacerbate the allergic inflammatory responses including eosinophils and cytokine production.


Assuntos
Imunossupressores/toxicidade , Metoxicloro/toxicidade , Paration/toxicidade , Efeitos Tardios da Exposição Pré-Natal/imunologia , Hipersensibilidade Respiratória/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas , Sinergismo Farmacológico , Eosinófilos , Feminino , Linfonodos/citologia , Linfonodos/imunologia , Metoxicloro/administração & dosagem , Camundongos Endogâmicos BALB C , Paration/administração & dosagem , Anidridos Ftálicos/imunologia , Gravidez , Hipersensibilidade Respiratória/imunologia
19.
Inflammation ; 42(3): 961-972, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30715691

RESUMO

Birch pollen allergy is a common cause of spring pollinosis in China. However, there is little research on birch pollen allergen in China and only the major allergen (Bet v 1) has been fully characterized. Chinese birch pollen-induced airway inflammation models in BALB/c mice were developed and administered subcutaneous immunotherapy (SCIT). BALB/c mice were sensitized subcutaneously on days 1, 8, and 15 with 25 µg/µL birch pollen extract. On days 24-26, the mice were challenged with 0.1% birch pollen aerosol. To investigate the efficacy of SCIT, mice were subcutaneously injected 0.3 mg birch pollen extract (BPE) with or without being adsorbed to alum. Airway hyper-responsiveness (AHR) to methacholine and immunological parameters was detected. Western blot analysis was applied with mice serum and mass spectrometry was used to identify the IgE-binding bands in birch pollen. Compared with PBS group, birch pollen sensitization and challenge BALB/c mice developed AHR, and IL4, IL5, IL6, IL10, and IL17 were significantly higher. Mice sensitized by birch pollen showed increased plasma levels of anti-BPE IgE, IgG1, and IgG2a. Histologic analyses showed that mice had peribranchial infiltration of inflammatory cells and mucosal hyperplasia. After SCIT, allergic symptoms effectively alleviated and kept for a long time. Interestingly, mice serum pool showed strong reactions to 70-kDa proteins. Mass spectrometry data suggests that the 70-kDa protein belongs to the HSP 70 family. SCIT inhibited the inflammatory response in the long term and a 70-kDa protein potentially belonging to the HSP 70 family plays a significant role in Chinese birch pollen-induced mice model.


Assuntos
Betula/imunologia , Imunoterapia/métodos , Rinite Alérgica Sazonal/terapia , Animais , China , Proteínas de Choque Térmico HSP70/análise , Inflamação/terapia , Espectrometria de Massas , Camundongos Endogâmicos BALB C , Hipersensibilidade Respiratória/imunologia , Rinite Alérgica Sazonal/etiologia
20.
Dermatitis ; 30(1): 62-66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30640765

RESUMO

BACKGROUND: Atopic dermatitis (AD) associated with respiratory atopy may represent a form of systemic contact dermatitis (SCD), whereby AD flares after ingestion or inhalation of allergens. OBJECTIVE: The aim of the study was to compare the prevalence of positive patch tests to allergens known to cause SCD in AD patients with and without respiratory atopy. METHODS: This is a retrospective study of patients with AD patch tested to 23 allergens known to cause SCD. Positive patch tests were compared between AD patients with and without respiratory atopy, stratified by age and wet or dry work occupation. CONCLUSIONS: Children and adolescents, but not adults, with AD and respiratory atopy were more likely than age-matched AD patients without respiratory atopy to have positive patch tests to these allergens (odds ratio, 2.33; 95% confidence interval, 1.13-4.79). Moreover, AD patients with respiratory atopy and engaging in wet work, but not dry work, occupations were more likely than AD patients without respiratory atopy to have positive patch tests to allergens known to cause SCD (odds ratio, 1.47; 95% confidence interval, 1.05-2.06). Thus, respiratory atopy and wet work are associated with sensitization to allergens known to cause SCD in patients with AD, and patch testing may be valuable in identifying systemic triggers of dermatitis in these patients.


Assuntos
Alérgenos/efeitos adversos , Asma/epidemiologia , Dermatite Alérgica de Contato/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Rinite Alérgica/epidemiologia , Adolescente , Adulto , Asma/imunologia , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/imunologia , Feminino , Humanos , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/imunologia , Imunização , Masculino , Razão de Chances , Testes do Emplastro , Prevalência , Hipersensibilidade Respiratória/epidemiologia , Hipersensibilidade Respiratória/imunologia , Estudos Retrospectivos , Rinite Alérgica/imunologia , Adulto Jovem
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