RESUMO
This study aimed to determine whether fucoxanthin alleviated ovalbumin (OVA)-induced food allergy (FA) and explored the possible mechanisms. The results indicated that supplementation with fucoxanthin at 10.0-20.0 mg/kg per day for 7 weeks inhibited food anaphylaxis and the production of immunoglobulin (Ig) E, IgG, histamine, and related cytokines while alleviating allergic symptoms in sensitized mice. Fucoxanthin enhanced the intestinal epithelial barrier by up-regulating tight junction (TJ) protein expression and promoting regenerating islet-derived protein III-gamma (RegIIIγ) and secretory IgA (sIgA) secretion. In addition, fucoxanthin induced the secretion of anti-inflammatory factors (interleukin (IL)-10 and transforming growth factor ß (TGF-ß)) by regulatory T (Treg) cells and decreased the pro-inflammatory factor levels (IL-4, tumor necrosis factor-α (TNF-α), IL-17, and IL-1ß), ameliorating intestinal inflammation. Compared with the model group, beneficial bacteria, such as Lactobacillaceae, increased in the intestinal flora, while pathogenic bacteria like Helicobacteraceae, Desulfovibrionaceae, and Streptococcaceae decreased. Therefore, fucoxanthin may effectively prevent FA by enhancing the intestinal epithelial barrier and reshaping the intestinal flora.
Assuntos
Hipersensibilidade Alimentar , Microbioma Gastrointestinal , Animais , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/prevenção & controle , Imunoglobulina E/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/metabolismo , XantofilasRESUMO
Bee pollen as a plant-derived food is consumed as nutritional/functional supplements by humans. But it might confer foodborne allergenicity in susceptible populations, limiting its extensive application. In this study, five potential allergens including profilin, cystatin, prolamin, expansin, and alcohol dehydrogenase in bee pollen derived from Brassica campestris (BP-Bc), were identified through mass spectrometry-based proteomic analysis. Moreover, different types of enzymes (cellulases, pectases, and papains) serve biological roles in pollen wall breaking and expansion, but also promote allergen release and degradation. Proteomic analysis showed that profilin, cystatin, and alcohol dehydrogenase were significantly reduced in BP-Bc following joint treatment with three enzymes. Metabolomic characterization of potential enzymatic hydrolysates of these significantly-decreased allergens was performed, which showed nine major oligopeptides and six amino acids at significantly higher levels in the enzyme-treated BP-Bc. These findings clarified the culprit responsible for bee pollen allergy and the mechanism of enzymatic desensitization for its further development.
Assuntos
Alérgenos , Hipersensibilidade Alimentar , Álcool Desidrogenase , Alérgenos/química , Animais , Abelhas , Hipersensibilidade Alimentar/metabolismo , Metabolômica/métodos , Pólen/química , Profilinas/química , Proteômica/métodosRESUMO
BACKGROUND: Non-specific lipid transfer proteins (LTPs) are important allergens in fruits, pollen, vegetables, nuts and latex. Due to their compact structure, LTPs are highly resistant to heat treatment. Here, Art v 3 from mugwort pollen and Pru p 3 from peach were used as model allergens to in-depth investigate structural and immunological properties upon thermal treatment at different buffer conditions. METHODS: Recombinant Art v 3 and Pru p 3 were purified from E. coli and incubated at 95⯰C up to 120â¯min using sodium phosphate buffer pH 3.4 or 7.3. Physicochemical properties of allergens were analyzed in circular dichroism spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering, size exclusion chromatography, and mass spectrometry. The crystal structure of Art v 3.0201 was determined to 1.9â¯Å resolution. IgG and IgE binding was investigated in ELISA using murine and LTP allergic patients' sera. RESULTS: Highly pure and homogenous recombinant allergens were obtained from bacterial production. The crystal structure of Art v 3.0201 revealed an antiparallel four helix bundle with a C-terminal extension mediating an asymmetric, transient dimer interface and differently sized cavities. Both allergens showed high thermal stability at acidic conditions. In contrast, extensive heat treatment in neutral buffer induced irreversible structural changes due to lanthionine-based cysteine rearrangement. This fostered loss of the typical α-helical structure, increased molecular size and abrogation of IgG and IgE binding epitopes. Pru p 3 lost its structural integrity at shorter heat stress duration than Art v 3, which did however only partially affect the molecule's IgE binding epitopes. CONCLUSION: During thermal treatment, susceptibility to structural changes of the LTP-fold is highly dependent on the surrounding environment but also on intrinsic features of individual LTPs. This is a crucial fact to consider when processing LTP-containing food or food products as this will directly influence their allergenic potential.
Assuntos
Alanina/análogos & derivados , Antígenos de Plantas/metabolismo , Proteínas de Transporte/metabolismo , Cisteína/metabolismo , Proteínas de Plantas/metabolismo , Sulfetos/metabolismo , Alanina/metabolismo , Sequência de Aminoácidos , Animais , Artemisia/metabolismo , Reações Cruzadas/fisiologia , Epitopos/metabolismo , Escherichia coli/metabolismo , Hipersensibilidade Alimentar/metabolismo , Humanos , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Camundongos , Pólen/metabolismo , Prunus/metabolismoRESUMO
Soluble CD14 (sCD14) is one of the immunomodulatory factors in breast milk (BM). Although it may be involved in the prevention of atopic symptoms and sensitization to both food and inhalant allergens, conflicting evidence exists concerning its protective effects. In this study, we investigated the relationship between sCD14 in colostrum and 1-month BM, and the development of atopic dermatitis (AD) and sensitization to food and aeroallergens at 9 months of age in infants who were exclusively or almost exclusively breastfed up to 4 months of age. BM samples were collected from lactating mothers who participated in a 2 × 2 factorial, randomized, nontreatment controlled trial study set in Tokyo, which looked at the efficacy of emollients and synbiotics in preventing AD and food allergy in children during the first year of life. A total of 258 colostrum samples and 269 1-month BM samples were analyzed. We found that one-month BM sCD14 levels in the AD group were significantly lower than in the non-AD group. Levels of sCD14 in 1-month BM were not related to allergen sensitization in the overall analysis, but egg white sensitization correlated inversely with 1-month BM sCD14 in infants without AD. The results suggest that sCD14 in BM may be involved in atopic manifestations in early infancy.
Assuntos
Aleitamento Materno , Dermatite Atópica/prevenção & controle , Hipersensibilidade Alimentar/prevenção & controle , Receptores de Lipopolissacarídeos/imunologia , Leite Humano/imunologia , Adulto , Fatores Etários , Colostro/imunologia , Colostro/metabolismo , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Feminino , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Humanos , Lactente , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Leite Humano/metabolismo , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , TóquioRESUMO
Hazelnut is one of the most frequent causes of food allergy. The major hazel allergen in Northern Europe is Cor a 1, which is homologous to the major birch pollen allergen Bet v 1. Both allergens belong to the pathogenesis related class PR-10. We determined the solution structure of Cor a 1.0401 from hazelnut and identified a natural ligand of the protein. The structure reveals the protein fold characteristic for PR-10 family members, which consists of a seven-stranded antiparallel ß-sheet, two short α-helices arranged in V-shape and a long C-terminal α-helix encompassing a hydrophobic pocket. However, despite the structural similarities between Cor a 1 and Bet v 1, they bind different ligands. We have shown previously that Bet v 1 binds to quercetin-3-O-sophoroside. Here, we isolated Cor a 1 from hazel pollen and identified the bound ligand, quercetin-3-O-(2"-O-ß-D-glucopyranosyl)-ß-D-galactopyranoside, by mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). NMR experiments were performed to confirm binding. Remarkably, although it has been shown that PR-10 allergens show promiscuous binding behaviour in vitro, we can demonstrate that Cor a 1.0401 and Bet v 1.0101 exhibit highly selective binding for their specific ligand but not for the respective ligand of the other allergen.
Assuntos
Antígenos de Plantas/metabolismo , Corylus/metabolismo , Proteínas de Plantas/metabolismo , Pólen/metabolismo , Algoritmos , Alérgenos/química , Alérgenos/genética , Alérgenos/metabolismo , Sequência de Aminoácidos , Antígenos de Plantas/química , Antígenos de Plantas/genética , Corylus/genética , Corylus/imunologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Galactose/química , Galactose/metabolismo , Ligantes , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Modelos Moleculares , Estrutura Molecular , Proteínas de Plantas/química , Proteínas de Plantas/genética , Pólen/imunologia , Ligação Proteica , Conformação Proteica , Homologia de Sequência de AminoácidosRESUMO
N-3 long chain polyunsaturated fatty acids (LCPUFAs) are considered to possess protective properties for human health by impacting on immunological reactions. An "inflammation-suppressive" effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as (food) allergy. LCPUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy in pre-clinical models. In this review, we explore the anti-allergic properties of LCPUFAs by providing an overview of clinical, in vivo and in vitro studies. Furthermore, we discuss the susceptibility of LCPUFAs to lipid oxidation and possible strategies to support the efficacy of LCPUFAs in reducing the allergy risk by using additional components with anti-oxidative and anti-inflammatory capacities such as the flavonoid quercetin. Finally, we propose new strategies to prevent (food) allergy using combinations of LCPUFAs and additional nutrients in diets or supplements, and postulate to investigate the use of LCPUFAs in allergic symptom relief.
Assuntos
Alérgenos/imunologia , Gorduras Insaturadas na Dieta/administração & dosagem , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/prevenção & controle , Animais , Suplementos Nutricionais , Hipersensibilidade Alimentar/metabolismo , Humanos , Imunização , Imunomodulação/efeitos dos fármacos , Peroxidação de LipídeosRESUMO
Food allergy prevalence is increasing all over the world. Recent epidemiologic studies have shown the link between vitamin D3 insufficiency and food allergy occurrence. In this study, we investigated the effect of supplementation with cholecalciferol, a widely used form of vitamin D3, on food allergy using an experimental mouse model. In wild-type BALB/c mice which were sensitized and challenged with an experimental allergen, ovalbumin, a clinical symptom of food allergy, diarrhea, was significantly induced with the elevation of immunoglobulin E level and the increases of T helper 2 cytokine productions, such as interleukin-4, -5, and -13 (p<0.05), whereas no change in T helper 1 cytokine production, such as interferon-γ, was observed. It was also found that cell population of CD69+ CD4+ T cells was increased slightly in spleen and significantly in the mesenteric lymphnode with the diarrheal symptom (p<0.05). Treatment of cholecalciferol reduced the allergic diarrhea (p<0.05) with the decreasing tendency of CD69+ CD4+ T cells, suggesting that the cell population might be associated with the attenuating effect of cholecalciferol on diarrhea occurrence, although immunoglobulin E levels and cytokine productions were not significantly altered by the treatment of cholecalciferol. When given the mice anti-CD69 mAb treatment, significant improvement of allergic diarrhea symptom was observed (p<0.05), accompanying the decrease of CD69+ CD4+ T cells which suggested the contribution of these cells to the diarrhea symptom. Taken together, we suggest that administration of cholecalciferol might be useful to suppress symptomatic food allergy in association with the decrease of CD69+ CD4+ T cells.
Assuntos
Antígenos CD , Antígenos de Diferenciação de Linfócitos T , Linfócitos T CD4-Positivos , Colecalciferol/farmacologia , Hipersensibilidade Alimentar , Lectinas Tipo C , Animais , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Citocinas/análise , Citocinas/metabolismo , Diarreia/imunologia , Diarreia/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismoRESUMO
The prevalence of allergic diseases such as allergic rhinitis, asthma, food allergy, and atopic dermatitis has increased dramatically during the last decades, which is associated with altered environmental exposures and lifestyle practices. The purpose of this review was to highlight the potential role for dietary fatty acids, in the prevention and management of these disorders. In addition to their nutritive value, fatty acids have important immunoregulatory effects. Fatty acid-associated biological mechanisms, human epidemiology, and intervention studies are summarized in this review. The influence of genetics and the microbiome on fatty acid metabolism is also discussed. Despite critical gaps in our current knowledge, it is increasingly apparent that dietary intake of fatty acids may influence the development of inflammatory and tolerogenic immune responses. However, the lack of standardized formats (ie, food versus supplement) and standardized doses, and frequently a lack of prestudy serum fatty acid level assessments in clinical studies significantly limit our ability to compare allergy outcomes across studies and to provide clear recommendations at this time. Future studies must address these limitations and individualized medical approaches should consider the inclusion of specific dietary factors for the prevention and management of asthma, food allergy, and atopic dermatitis.
Assuntos
Asma/metabolismo , Dermatite Atópica/metabolismo , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Hipersensibilidade Alimentar/metabolismo , Adulto , Fatores Etários , Animais , Asma/epidemiologia , Asma/etiologia , Asma/prevenção & controle , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Dermatite Atópica/prevenção & controle , Modelos Animais de Doenças , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/prevenção & controle , Humanos , Imunomodulação , Lactente , Recém-Nascido , Metabolismo dos Lipídeos , Transdução de SinaisRESUMO
We are now in the epoch of "molecular allergology" and numerous clinically relevant allergenic molecules are available improving the performance of in vitro allergen tests and allergen detection methods. This review is focusing on characterized occupational allergens and their implementation into the in vitro diagnosis for occupational allergy and in allergen detection methods. More than 400 occupational agents are identified and documented as being 'respiratory sensitizers', but currently only a limited number of them are characterized on the molecular level and available for routine diagnosis as native or recombinant allergens. One exception, however, is natural rubber latex (NRL) from Hevea brasiliensis still remaining an important occupational allergen source. Characterization of 15 NRL allergens led to the development of assays for the determination of allergen content of NRL materials and the implementation of component-resolved diagnosis (CRD) for specific IgE antibody measurement. Microarray or singleplex using recombinant or native allergens are reliable tools for NRL allergy diagnosis. In addition, NRL allergy is an excellent model for improving extract-based specific IgE measurement by amplification of NRL extract preparation with stable recombinant major allergen rHev b 5. Despite the many efforts to characterize the occupationally relevant wheat allergens for baker's asthma, the most frequently occurring forms of occupational asthma, the results are highly diverse. Wheat sensitization profiles of bakers showed great interindividual variability and no wheat allergen could be classified as the major allergen. For diagnosis of baker's asthma, a whole wheat extract is still the best option for specific IgE determination. But single wheat allergens might help to discriminate between wheat-induced food allergy, grass pollen allergy and baker's asthma. For workplace-related allergens like coffee, wood, soybean, seafood and moulds allergens are characterized and few of them are available, but their relevance for occupational sensitization routes should be verified in the further studies.
Assuntos
Alérgenos/imunologia , Asma Ocupacional/imunologia , Animais , Hipersensibilidade Alimentar/metabolismo , Humanos , Imunoglobulina E/imunologia , Hipersensibilidade ao Látex/imunologia , Pólen/imunologiaRESUMO
BACKGROUND: People's preference for fish with a high trophic level, like Atlantic cod and tuna, leads to a large food footprint. Responsible seafood consumption should include underutilised local products; hence the culinary use of edible jellyfish can be an effective contribution. The present work focused on Catostylus tagi to contribute to the consumption of edible jellyfish in the West. RESULTS: A questionnaire conducted with 192 young people showed an interest in tasting jellyfish-based food (64.6%). The resulting product, obtained by an alternative cooking process to traditional Asian ones, was chemically characterised and underwent microbiological and heavy metals control. The results indicated its non-toxicity. Patients who were allergic to seafood as well as non-allergic volunteers revealed no allergic reaction to the jellyfish umbrella product (intakes up to 5 mg/kg body weight and 8 mg/kg, respectively). Seafood-trained panellists defined the product's main impact on the mouth as freshness (72 mg/kg body weight). The preliminary snack, a pâté, was positively accepted by allergic (7 in 9; n = 20) and non-allergic volunteers (6 in 7; n = 21). CONCLUSION: The present study confirmed that jellyfish intake is safe, even for allergic individuals, and its organoleptic properties were accepted by the study population. © 2018 Society of Chemical Industry.
Assuntos
Cifozoários/química , Alimentos Marinhos/análise , Adulto , Animais , Segurança Química , Culinária , Ingestão de Alimentos , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/fisiopatologia , Inocuidade dos Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cifozoários/imunologia , Cifozoários/metabolismo , PaladarRESUMO
Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels. We therefore hypothesized that desensitization by low-dose immunotherapy is associated with reduced influx of calcium ions into lymphocytes. The aim of this study was to test this hypothesis. Methods Intracellular lymphocytic calcium ion concentrations were assayed in a total of 47 patients, following incubation with picogram amounts of the test allergens, using a cell-permeable calcium-sensing ratiometric fluorescent dye and fluorescence spectroscopy, both at baseline and following successful provocation neutralization treatment with low-dose immunotherapy. Results Low-dose immunotherapy was associated with a reduction in lymphocytic intracellular calcium ion concentration following treatment of: 23â% for metabisulfite sensitivity (p<0.0004); 12â% for salicylate sensitivity (p<0.01); 23â% for benzoate sensitivity (p<0.01); 30â% for formaldehyde sensitivity (p<0.0001); 16â% for sensitivity to petrol exhaust (p<0.003); 16â% for natural gas sensitivity (p<0.001); 13â% for nickel sensitivity (p<0.05); 30â% for sensitivity to organophosphates (p<0.01); and 24â% for sensitivity to nitrosamines (p<0.05). Conclusions Low-dose immunotherapy may affect baseline levels of intracellular calcium in lymphocytes, supporting the premise that allergens affect cell signaling in immune cells and provocation neutralization immunotherapy helps to promote more normal immune cell signaling.
Assuntos
Alérgenos , Cálcio/metabolismo , Dessensibilização Imunológica , Doença Ambiental/terapia , Linfócitos/metabolismo , Adulto , Benzoatos/efeitos adversos , Doença Ambiental/metabolismo , Feminino , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/terapia , Formaldeído/efeitos adversos , Humanos , Masculino , Sensibilidade Química Múltipla/metabolismo , Sensibilidade Química Múltipla/terapia , Gás Natural/efeitos adversos , Níquel/efeitos adversos , Nitrosaminas/efeitos adversos , Organofosfatos/efeitos adversos , Salicilatos/efeitos adversos , Emissões de VeículosRESUMO
The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy.
Assuntos
Modelos Animais de Doenças , Flavanonas/farmacologia , Hipersensibilidade Alimentar/prevenção & controle , Intestinos/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Fitoterapia , Extratos Vegetais/farmacologia , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/imunologia , Receptores de Hidrocarboneto Arílico/metabolismo , Scutellaria baicalensis/química , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/imunologia , Junções Íntimas/metabolismoRESUMO
The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.
Assuntos
Dermatite Atópica/tratamento farmacológico , Hipersensibilidade Alimentar/tratamento farmacológico , Imunossupressores/uso terapêutico , Extratos Vegetais/uso terapêutico , Wolfiporia/química , Animais , Linfócitos T CD4-Positivos/metabolismo , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Casca de Planta , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) during the suckling period on the development of the immune system and oral tolerance (OT) in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA) or DHA (N = 8, 0.9% DHA) diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA) treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13) response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05). Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-ß production after stimulation with OVA (all p < 0.05). Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05). Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT.
Assuntos
Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Hipersensibilidade Alimentar/prevenção & controle , Tolerância Imunológica/efeitos dos fármacos , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Ovalbumina/imunologia , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , Proteínas do Ovo , Feminino , Hipersensibilidade Alimentar/metabolismo , Imunoglobulina E/sangue , Interleucina-10/metabolismo , Gravidez , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/metabolismo , Linfócitos T/metabolismo , Equilíbrio Th1-Th2 , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Food allergies affect 4-8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice. METHODS: After weaning, the offspring from mothers that were exposed to GOS/inulin mixture or fed a control diet were intraperitoneally sensitized to wheat proteins to induce a systemic allergic response and orally exposed to the same allergen. Immunological, physiological, and microbial parameters were analyzed. RESULTS: GOS/inulin mixture diet modified the microbiota of mothers and their offspring. Offspring from mothers that received GOS/inulin prebiotics were protected against food allergies and displayed lower clinical scores, specifically of IgE and histamine levels, compared to offspring from mothers fed a control diet. Moreover, GOS/inulin supplementation for the mother resulted in stronger intestinal permeability in the offspring. Enhancement of the regulatory response to allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response were observed in mice from GOS/inulin mixture-exposed mothers. CONCLUSION: The treatment of pregnant and lactating mice with nondigestible GOS/inulin prebiotics promotes a long-term protective effect against food allergies in the offspring.
Assuntos
Hipersensibilidade Alimentar/prevenção & controle , Tolerância Imunológica , Inulina , Exposição Materna , Oligossacarídeos , Efeitos Tardios da Exposição Pré-Natal , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Inulina/administração & dosagem , Lactação , Camundongos , Microbiota , Oligossacarídeos/administração & dosagem , Permeabilidade , Gravidez , Células Th2/imunologia , Células Th2/metabolismoRESUMO
Trachelospermi caulis is used widely as an herbal medicine in oriental countries to attenuate fever and pain. We wished to reveal the novel function of this herb and its active component on barrier function in intestinal epithelial cells. Monolayers of intestinal epithelial cells (Caco-2) were used to evaluate the transepithelial electrical resistance (TEER) and quantity of permeated ovalbumin (OVA) as indices of barrier function. T. caulis increased TEER values on cell monolayers and decreased OVA permeation across cell monolayers. To ascertain the active component of T. caulis, the extract was isolated to five fractions, and the effect of each of these fractions on intestinal barrier function examined. Chloroform and ethyl acetate fractions showed increased TEER values and decreased OVA flux. Chloroform and ethyl acetate fractions contained mainly trachelogenin and its glycoside, tracheloside. Trachelogenin increased TEER values and decreased OVA flux by enhancing the tight-junction protein occludin (but not tracheloside) in Caco-2 monolayers. These findings demonstrated that trachelogenin, an active component of T. caulis, might help to attenuate food allergy or inflammatory bowel disease through inhibition of allergen permeation or enhancement of the intestinal barrier.
Assuntos
4-Butirolactona/análogos & derivados , Alérgenos/metabolismo , Apocynaceae/química , Colo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Junções Íntimas/efeitos dos fármacos , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Células CACO-2 , Colo/metabolismo , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/metabolismo , Glucosídeos/farmacologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Ocludina/metabolismo , Ovalbumina/metabolismo , Permeabilidade , Fitoterapia , Extratos Vegetais/uso terapêutico , Junções Íntimas/metabolismoRESUMO
IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.
Assuntos
Anafilaxia/tratamento farmacológico , Curcumina/uso terapêutico , Hipersensibilidade Alimentar/tratamento farmacológico , Mastocitose/tratamento farmacológico , Anafilaxia/imunologia , Anafilaxia/metabolismo , Animais , Curcumina/farmacologia , Modelos Animais de Doenças , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Mastocitose/imunologia , Mastocitose/metabolismo , Camundongos , NF-kappa B/metabolismo , Ovalbumina , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
ω3 polyunsaturated fatty acids (PUFAs) have anti-allergic and anti-inflammatory properties, but the immune-metabolic progression from dietary oil remains to be investigated. Here we identified 17,18-epoxyeicostetraenoic acid (17,18-EpETE) as an anti-allergic metabolite generated in the gut from dietary ω3 α-linolenic acid (ALA). Biochemical and imaging mass spectrometry analyses revealed increased ALA and its metabolites, especially eicosapentaenoic acid (EPA), in the intestines of mice receiving ALA-rich linseed oil (Lin-mice). In murine food allergy model, the decreased incidence of allergic diarrhea in Lin-mice was due to impairment of mast cell degranulation without affecting allergen-specific serum IgE. Liquid chromatography-tandem mass spectrometry-based mediator lipidomics identified 17,18-EpETE as a major ω3 EPA-derived metabolite generated from dietary ALA in the gut, and 17,18-EpETE exhibits anti-allergic function when administered in vivo. These findings suggest that metabolizing dietary ω3 PUFAs generates 17,18-EpETE, which is an endogenous anti-allergic metabolite and potentially is a therapeutic target to control intestinal allergies.
Assuntos
Ácidos Graxos Ômega-3 , Hipersensibilidade Alimentar/tratamento farmacológico , Mucosa Intestinal/metabolismo , Óleo de Semente do Linho/farmacologia , Animais , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Feminino , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/patologia , Intestinos/patologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The present study aimed at analysing the content of fluorine (F), calcium (Ca), magnesium (Mg), iron (Fe) and zinc (Zn) in the drinks for children and infant formulas, a popular supplement or substitute for breast milk produced from cow milk on an industrial scale. Ca, Mg, Zn and Fe concentrations were determined using atomic absorption spectrophotometer, while F levels using a potentiometric method. F levels in the examined formula samples increased with the intended age range, until the intended age of 1 year, and then decreased. A lower content of Ca, Mg and Zn was observed in formulas intended for children <1 year of age and higher for older children. Fe content increased with the age range. A statistically significant higher content of Ca, Mg, Zn and Fe in samples intended for children with phenylketonuria in comparison to those intended for healthy children or children with food allergies was noted. The content of the analysed elements in juices and nectars showed the highest contents in products intended for infants (under 6 months of age). The lowest levels of elements tested were found in drinks for children over 6 months of age. In conclusion, the concentrations of the examined elements in infant formulas and juices for children were decidedly greater than the standards for the individual age groups. Although the absorption of these elements from artificial products is far lower than from breast milk, there is still the fear of consequences of excessive concentrations of these minerals.
Assuntos
Bebidas/análise , Fórmulas Infantis/química , Minerais/metabolismo , Necessidades Nutricionais , Adolescente , Fatores Etários , Animais , Cálcio/metabolismo , Bovinos , Criança , Ciências da Nutrição Infantil/métodos , Ciências da Nutrição Infantil/normas , Pré-Escolar , Hipersensibilidade Alimentar/metabolismo , Humanos , Lactente , Recém-Nascido , Ferro/metabolismo , Magnésio/metabolismo , Leite/química , Leite Humano/química , Fenilcetonúrias/metabolismo , Potenciometria , Espectrofotometria Atômica , Zinco/metabolismoRESUMO
Allergen-IgE complexes are more efficiently internalized and presented by B cells than allergens alone. It has been suggested that IgG Abs induced by immunotherapy inhibit these processes. Food-allergic patients have high allergen-specific IgG levels. However, the role of these Abs in complex formation and binding to B cells is unknown. To investigate this, we incubated sera of peanut- or cow's milk-allergic patients with their major allergens to form complexes and added them to EBV-transformed or peripheral blood B cells (PBBCs). Samples of birch pollen-allergic patients were used as control. Complex binding to B cells in presence or absence of blocking Abs to CD23, CD32, complement receptor 1 (CR1, CD35), and/or CR2 (CD21) was determined by flow cytometry. Furthermore, intact and IgG-depleted sera were compared. These experiments showed that allergen-Ab complexes formed in birch pollen, as well as food allergy, contained IgE, IgG1, and IgG4 Abs and bound to B cells. Binding of these complexes to EBV-transformed B cells was completely mediated by CD23, whereas binding to PBBCs was dependent on both CD23 and CR2. This reflected differential receptor expression. Upon IgG depletion, allergen-Ab complexes bound to PBBCs exclusively via CD23. These data indicated that IgG Abs are involved in complex formation. The presence of IgG in allergen-IgE complexes results in binding to B cells via CR2 in addition to CD23. The binding to both CR2 and CD23 may affect Ag processing and presentation, and (may) thereby influence the allergic response.