Environmental epigenetics of asthma: An update

Ho, Shuk‐Mei

doi:10.1016/j.jaci.2010.07.030

Cited by 196 publications

(176 citation statements)

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“…Moreover, some genetic variants of TSLP have been linked to asthma or allergic rhinitis [78]. The altered genes that appeared in exposed individuals have been implicated in pulmonary effects driven by environmental agents such as viruses, cigarette smoke, oxidants, and air pollution [79][80][81], explaining, in part, the higher susceptibility of these patients to the action of airborne insults (see below).…”

Section: Airway Epithelium As a Key Player In Orchestrating The Allermentioning

confidence: 99%

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

López-Rodríguez

Benedé

Barderas

et al. 2017

J Investig Allergol Clin Immunol

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Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease. Key words: Airway epithelium. Barrier dysfunction. Respiratory allergy. Redox biology. Air pollutants. ResumenEl epitelio pulmonar constituye la barrera celular más susceptible a la acción deletérea de la multitud de agentes que se encuentran en el ambiente, incluidos los alérgenos. Además de prevenir su acceso al organismo, la barrera epitelial de las vías respiratorias juega un papel inmunomodulador crucial, regulando de forma local la acción de las células del sistema inmune subyacentes. Una disfunción epitelial, provocada tanto directa como indirectamente por la acción de los aeroalérgenos, parece ser una de las causas principales de desregulación de la homeostasis pulmonar, causando una respuesta proinflamatoria descontrolada que cada vez más autores atribuyen al origen de las reacciones alérgicas. En esta revisión se quiere destacar el papel de la barrera epitelial pulmonar como regulador de la respuesta inmune en el contexto de la alergia. Las enfermedades crónicas que afectan a las vías respiratorias, tales como el asma alérgica, muestran frecuentemente una función epitelial defectuosa, apoyando así la hipótesis antes mencionada que subyace al origen de la alergia. El impacto de otros contaminantes ambientales -como virus respiratorios, bacterias, humo del tabaco y partículas diésel-sobre la integridad epitelial, así como su influencia en la biología redox pulmonar relacionada con el desarrollo de la respuesta alérgica, también se abordarán en la presente revisión.

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Section: Airway Epithelium As a Key Player In Orchestrating The Allermentioning

confidence: 99%

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

López-Rodríguez

Benedé

Barderas

et al. 2017

J Investig Allergol Clin Immunol

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“…Studies in asthma are also leading to a new understanding of the role of environmental exposures in altering DNA methylation as well as histone modifications (reviewed in ref. 29). Twin studies in Alzheimer disease support the notion that epigenetic mechanisms mediate risk (reviewed in ref.…”

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confidence: 91%

DNA methylation in white blood cells

et al. 2011

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“…Individuals with asthma experience great difficulties in breathing and have reduced quality of life, with repeated visits to clinics or emergency rooms. It is well recognized that the development of asthma is related to a combination of genetic and environmental factors, but the precise mechanisms of pathogenesis in asthma are still unclear (1,2). There are many triggers of asthmatic attacks; most of them are associated with environmental exposure to allergens.…”

mentioning

confidence: 99%

Epigenetic Alterations by DNA Methylation in House Dust Mite–Induced Airway Hyperresponsiveness

Shang

Das

Rabold

et al. 2013

Am J Respir Cell Mol Biol

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Asthma is one of the most prevalent chronic lung diseases, affecting 235 million individuals around the world, with its related morbidity and mortality increasing steadily over the last 20 years. Exposure to the environmental allergen, house dust mite (HDM), results in airway inflammation with a variable degree of airway obstruction. Although there has been much experimental work in the past using HDM challenge models to understand mechanistic details in allergic inflammation and airway hyperresponsiveness (AHR), there has been no study on reprogramming of lung or airways mediated through epigenetic mechanisms in response to an acute HDM exposure. Male mice, 6 weeks of age, were administrated HDM extracts or saline at Days 1, 14, and 21. Exposure of mice to HDM extracts caused significant airway inflammation and increased AHR. These HDMchallenged mice also exhibited a change in global DNA methylation as compared with saline-exposed (control) mice. Next, by employing methylation-sensitive restriction fingerprinting, we identified a set of genes, showing aberrant methylation status, associated with the HDM-induced AHR. These candidate genes are known to be involved in cAMP signaling (pde4 d), Akt-signaling (akt1 s1), ion transport (tm6 sf1, pom121l2, and slc8a3), and fatty acid metabolism (acsl3). Slc8a3 and acsl3 were down-regulated, whereas pde4 d, akt1 s1, tm6 sf1, and pom121l2 were up-regulated in the mice exposed to HDM. Hence, our results suggest that HDM exposure induces a series of aberrant methylated genes that are potentially important for the development of allergic AHR.Keywords: airway hyperresponsiveness; DNA methylation; epigenetics; house dust mite Asthma is one of the most prevalent chronic lung diseases, affecting 235 million individuals around the world (www.who.int). Individuals with asthma experience great difficulties in breathing and have reduced quality of life, with repeated visits to clinics or emergency rooms. It is well recognized that the development of asthma is related to a combination of genetic and environmental factors, but the precise mechanisms of pathogenesis in asthma are still unclear (1, 2). There are many triggers of asthmatic attacks; most of them are associated with environmental exposure to allergens. In the inner city environment, house dust mite (HDM) allergy is reported to be the most prevalent cause of allergic sensitization in individuals with asthma (3). Exposure to HDM results in airway inflammation with a variable degree of airway obstruction. In animal studies, chronic exposure of mice to HDM leads to significant airway inflammation, increased airway hyperresponsiveness (AHR), and remodeling of bronchi (4-6). Even though much work has been done in the past using this HDM model to probe the immunologic pathways, there is no study addressing the epigenetic basis of how this environmental allergen "reprograms" the airways, thereby predisposing the animals to asthma.Epigenetics provide a promising approach for improving our understanding of complex diseases like asth...

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Environmental epigenetics of asthma: An update

Cited by 196 publications

References 173 publications

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

DNA methylation in white blood cells

Epigenetic Alterations by DNA Methylation in House Dust Mite–Induced Airway Hyperresponsiveness

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