Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Handb Exp Pharmacol ; 268: 331-357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34223997

RESUMO

There has been a substantial increase in the incidence and the prevalence of allergic disorders in the recent decades, which seems to be related to rapid environmental and lifestyle changes, such as higher exposure to factors thought to exert pro-allergic effects but less contact with factors known to be associated with protection against the development of allergies. Pollution is the most remarkable example of the former, while less contact with microorganisms, lower proportion of unprocessed natural products in diet, and others resulting from urbanization and westernization of the lifestyle exemplify the latter. It is strongly believed that the effects of environmental factors on allergy susceptibility and development are mediated by epigenetic mechanisms, i.e. biologically relevant biochemical changes of the chromatin carrying transcriptionally-relevant information but not affecting the nucleotide sequence of the genome. Classical epigenetic mechanisms include DNA methylation and histone modifications, for instance acetylation or methylation. In addition, microRNA controls gene expression at the mRNA level. Such epigenetic mechanisms are involved in crucial regulatory processes in cells playing a pivotal role in allergies. Those include centrally managing cells, such as T lymphocytes, as well as specific structural and effector cells in the affected organs, responsible for the local clinical presentation of allergy, e.g. epithelial or airway smooth muscle cells in asthma. Considering that allergic disorders possess multiple clinical (phenotypes) and mechanistic (endotypes) forms, targeted, stratified treatment strategies based on detailed clinical and molecular diagnostics are required. Since conventional diagnostic or therapeutic approaches do not suffice, this gap could possibly be filled out by epigenetic approaches.


Assuntos
Asma , Hipersensibilidade , Metilação de DNA , Epigênese Genética , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/genética , Hipersensibilidade/prevenção & controle , Processamento de Proteína Pós-Traducional
2.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067156

RESUMO

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.


Assuntos
Asma/metabolismo , Vesículas Extracelulares/metabolismo , Animais , Asma/genética , Asma/microbiologia , Asma/fisiopatologia , Biomarcadores/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos
3.
Nutrients ; 13(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668787

RESUMO

Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.


Assuntos
Epigênese Genética/imunologia , Hipersensibilidade , Fenômenos Fisiológicos da Nutrição do Lactente , Fenômenos Fisiológicos da Nutrição Materna , Feminino , Humanos , Recém-Nascido , Gravidez
4.
J Allergy Clin Immunol ; 146(4): 685-693, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33032723

RESUMO

Obesity has been well recognized as an important comorbidity in patients with asthma, representing a unique phenotype and endotype. This association indicates a close relationship between metabolic and inflammatory dysregulation. However, the detailed organ-organ, cellular, and molecular interactions are not completely resolved. Because of that, the relationship between obesity and asthma remains unclear. In this article, clinical and epidemiological studies, as well as data from experimental animal work, are being summarized to provide a state of the art update on this important topic. Much more work is needed, particularly mechanistic, to fully understand the interaction between obesity and asthma and to develop novel preventive and therapeutic strategies.


Assuntos
Asma/etiologia , Suscetibilidade a Doenças , Obesidade/complicações , Animais , Asma/epidemiologia , Asma/metabolismo , Asma/prevenção & controle , Comorbidade , Metabolismo Energético , Feminino , Predisposição Genética para Doença , Humanos , Modelos Animais , Obesidade/epidemiologia , Obesidade/etiologia , Obesidade/metabolismo , Vigilância da População , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores de Risco
5.
Nutrients ; 12(10)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086571

RESUMO

Immunoglobulin E (IgE)-mediated allergy against cow's milk protein fractions such as whey is one of the most common food-related allergic disorders of early childhood. Histone acetylation is an important epigenetic mechanism, shown to be involved in the pathogenesis of allergies. However, its role in food allergy remains unknown. IgE-mediated cow's milk allergy was successfully induced in a mouse model, as demonstrated by acute allergic symptoms, whey-specific IgE in serum, and the activation of mast cells upon a challenge with whey protein. The elicited allergic response coincided with reduced percentages of regulatory T (Treg) and T helper 17 (Th17) cells, matching decreased levels of H3 and/or H4 histone acetylation at pivotal Treg and Th17 loci, an epigenetic status favoring lower gene expression. In addition, histone acetylation levels at the crucial T helper 1 (Th1) loci were decreased, most probably preceding the expected reduction in Th1 cells after inducing an allergic response. No changes were observed for T helper 2 cells. However, increased histone acetylation levels, promoting gene expression, were observed at the signal transducer and activator of transcription 6 (Stat6) gene, a proallergic B cell locus, which was in line with the presence of whey-specific IgE. In conclusion, the observed histone acetylation changes are pathobiologically in line with the successful induction of cow's milk allergy, to which they might have also contributed mechanistically.


Assuntos
Histonas/metabolismo , Imunoglobulina E/imunologia , Hipersensibilidade a Leite/imunologia , Células Th1 , Acetilação , Animais , Linfócitos B/imunologia , Modelos Animais de Doenças , Epigenômica , Feminino , Expressão Gênica , Imunoglobulina E/sangue , Mastócitos/imunologia , Camundongos Endogâmicos C3H , Hipersensibilidade a Leite/genética , Fator de Transcrição STAT6 , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Soro do Leite/imunologia
6.
Front Immunol ; 11: 1747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973742

RESUMO

Asthma is a chronic inflammatory disease of the respiratory tract characterized by recurrent breathing problems resulting from airway obstruction and hyperresponsiveness. Human airway epithelium plays an important role in the initiation and control of the immune responses to different types of environmental factors contributing to asthma pathogenesis. Using pattern recognition receptors airway epithelium senses external stimuli, such as allergens, microbes, or pollutants, and subsequently secretes endogenous danger signaling molecules alarming and activating dendritic cells. Hence, airway epithelial cells not only mediate innate immune responses but also bridge them with adaptive immune responses involving T and B cells that play a crucial role in the pathogenesis of asthma. The effects of environmental factors on the development of asthma are mediated, at least in part, by epigenetic mechanisms. Those comprise classical epigenetics including DNA methylation and histone modifications affecting transcription, as well as microRNAs influencing translation. The common feature of such mechanisms is that they regulate gene expression without affecting the nucleotide sequence of the genomic DNA. Epigenetic mechanisms play a pivotal role in the regulation of different cell populations involved in asthma pathogenesis, with the remarkable example of T cells. Recently, however, there is increasing evidence that epigenetic mechanisms are also crucial for the regulation of airway epithelial cells, especially in the context of epigenetic transfer of environmental effects contributing to asthma pathogenesis. In this review, we summarize the accumulating evidence for this very important aspect of airway epithelial cell pathobiology.


Assuntos
Asma/genética , Asma/imunologia , Epigênese Genética , Células Epiteliais/imunologia , Pulmão/imunologia , Acetilação , Animais , Asma/metabolismo , Asma/fisiopatologia , Hiper-Reatividade Brônquica/genética , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/fisiopatologia , Broncoconstrição , Metilação de DNA , Células Epiteliais/metabolismo , Histonas/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/fisiopatologia , MicroRNAs/genética , MicroRNAs/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais
7.
Cell Signal ; 69: 109523, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31904412

RESUMO

The term (bronchial) asthma describes a disorder syndrome that comprises several disease phenotypes, all characterized by chronic inflammation in the bronchial epithelium, with a variety of subsequent functional consequences. Thus, the epithelium in the conducting airways is the main localization of the complex pathological changes in the disease. In this regard, bronchial epithelial cells are not passively affected by inflammatory mechanisms induced by immunological processes but rather actively involved in all steps of disease development from initiation and perpetuation to chronification. In recent years it turned out that bronchial epithelial cells show a high level of structural and functional diversity and plasticity with epigenetic mechanisms playing a crucial role in the regulation of these processes. Thus, it is quite reasonable that differential functional activities of the bronchial epithelium are involved in the development of different asthma phenotypes and/or stages of disease. The current knowledge on this topic will be discussed in this review article.


Assuntos
Asma , Brônquios , Células Epiteliais , Inflamação , Animais , Asma/metabolismo , Asma/patologia , Brônquios/metabolismo , Brônquios/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Epitélio/metabolismo , Epitélio/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia
8.
Pol Arch Intern Med ; 128(7-8): 469-477, 2018 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-30057383

RESUMO

Asthma is a widespread chronic inflammatory disease, which has a highly heterogeneous etiopathogenesis, with predominance of either T­helper cell type 2 (Th2; type 2) or non-Th2 (non-type 2) mechanisms. Together with cardiovascular or autoimmune diseases, obesity, and others, asthma belongs to so called noncommunicable diseases, a group of disorders with immunometabolic links as underlying mechanisms. So far, obesity and asthma have been considered mostly independently, but there are clear signs of relevant interactions. First, obese patients are at increased risk of asthma or asthma­like symptoms. Second, asthma accompanied by obesity is more severe and more difficult to treat. A specific phenotype called obesity­associated asthma has been also described, which is late­onset, rather severe, non-type 2­driven disease, present mostly in women. In addition, obesity can coincide with asthma also in children, and, although obesity generally skews the Th1/Th2 balance towards Th1, it can also accompany type 2­driven asthma. However, those combinations represent less precisely defined disease entities. Despite a substantial increase in our knowledge on the mechanisms mediating the effects of obesity on the development of asthma in several recent years, still much needs to be done, especially on the molecular level.


Assuntos
Asma/etiologia , Obesidade/complicações , Adipocinas , Asma/complicações , Asma/epidemiologia , Feminino , Humanos , Masculino , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...