Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice

Fischer, Kimberly D.; Hall, Sannette C.; Agrawal, Devendra K.

doi:10.1371/journal.pone.0149180

Cited by 42 publications

(35 citation statements)

References 44 publications

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“…Further examination of the airways in mice that were fed a diet supplemented with 10,000 IU/kg of vitamin D showed increased expression of E-cadherin and decreased expression of vimentin and N-cadherin in airway epithelial cells. 20 …”

Section: Results From Animal Studiesmentioning

confidence: 99%

Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years

Hall

Agrawal

2017

Clinical Therapeutics

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101

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Vitamin D is a potent immunomodulator capable of dampening inflammatory signals in several cell types involved in the asthmatic response. Its deficiency has been associated with increased inflammation, exacerbations and overall worse outcomes in patients with asthma. Given the increase in the prevalence of asthma over the last few decades, there has been enormous interest in the use of vitamin D supplementation as a potential therapeutic option. Several studies have found that low serum levels of vitamin D (< 20 ng/ml) are associated with increased exacerbations, increased airway inflammation, decreased lung function and poor prognosis in asthmatic patients. Results from the in vitro and in vivo studies in animals and human have suggested that supplementation with vitamin D can ameliorate several hallmark features of asthma. However, the findings obtained from clinical trials are controversial and do not unequivocally support the beneficial role of vitamin D in asthma. Largely, interventional studies in children, pregnant women and adults have primarily found little-to-no effect of vitamin D supplementation on improved asthma symptoms, onset or progression of the disease. This could be related to the severity of the disease process and other confounding factors. Despite the conflicting data obtained from clinical trials, vitamin D deficiency does influence the inflammatory response in the airways. Further studies are needed to determine the exact mechanisms by which vitamin D supplementation may induce anti-inflammatory effects. Here, we critically reviewed the most recent findings from in vitro studies, animal models, and clinical trials regarding the role of vitamin D in bronchial asthma.

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Section: Results From Animal Studiesmentioning

confidence: 99%

Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years

Hall

Agrawal

2017

Clinical Therapeutics

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101

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“…In murine models, vitamin D deficiency is associated with airway hyper-responsiveness (AHR), as well as with increased pro-inflammatory cytokines and reduced T-regulatory (T-reg) cells in bronchoalveolar lavage fluid (BALF) 33 . Moreover, vitamin D supplementation attenuates allergen-induced inflammation and AHR in sensitized mice 33,34 . Among children, three common genetic variants in the class I MHC–restricted T cell–associated molecule gene (CRTAM) have been associated with asthma exacerbations in those with vitamin D deficiency 35 , and polymorphisms in the gene for the vitamin D receptor have been associated with asthma 365 .…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Insufficiency and Asthma in a US Nationwide Study

Han

Forno

Celedón

2017

The Journal of Allergy and Clinical Immunology: In Practice

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Background Vitamin D insufficiency (a serum 25(OH)D < 30 ng/ml) has been associated with asthma morbidity. Objective To examine vitamin D insufficiency, asthma and lung function among U.S. children and adults. Methods Using data from NHANES for 2001–2010, we examined vitamin D insufficiency and: 1) current asthma or wheeze in 10,860 children (6–17 years) and 24,115 adults (18–79 years), and 2) lung function in a subset of participants. Logistic or linear regression was used for the multivariable analysis, adjusting for age, gender, race/ethnicity, income, body mass index, smoking, and C-reactive protein level. Results Vitamin D insufficiency was associated with current asthma (odds ratio [OR]=1.35, 95% confidence interval [CI]=1.11–1.64) and current wheeze in children, as well as with current wheeze in adults (OR=1.17, 95%CI=1.04–1.31). After stratifying the analysis by race/ethnicity and (in adults) current smoking, vitamin D insufficiency was associated with current asthma and wheeze in non-Hispanic white children only; in adults, vitamin D insufficiency was associated with current wheeze in non-Hispanic whites and blacks. Vitamin D insufficiency was also associated with lower FEV1 and FVC in children and adults. When analyzing each NHANES wave separately, vitamin D insufficiency prevalence was 72%–76% from 2001 to 2006, and then decreased from 2007 to 2010 (64%–65%); interestingly, asthma prevalence decreased for the first time from 2007–2008 (8.2%) to 2009–2010 (7.4%). Conclusions We show racial/ethnic-specific associations between vitamin D insufficiency and current asthma or wheeze in children and adults. Moreover, we report parallel recent decrements in the prevalence of vitamin D insufficiency and asthma.

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“…A multitude of dietary factors have the capacity to alter epithelial behavior via direct receptor action or indirect regulation of tissue metabolism. For example, Fischer et al demonstrated that vitamin D supplementation, acting via the vitamin D receptor pathway, reduces EMT processes and improves barrier function in several clinically relevant murine models of asthma 89 . Fatty acid-deficient diets spontaneously induce skin barrier disruption via alteration of skin metabolism 90, 91 .…”

Section: Mechanisms Of Barrier Defectsmentioning

confidence: 99%

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

141

122

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Epithelial barriers of the skin, gastrointestinal tract and airway serve common critical functions such as maintaining a physical barrier against environmental insults and allergens, as well as providing a tissue interface balancing the communication between the internal and external environments. We now understand that in allergic disease, regardless of tissue location, the homeostatic balance of the epithelial barrier is skewed towards loss of differentiation, reduced junctional integrity and impaired innate defense. Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease. Despite our growing appreciation of the centrality of barrier dysfunction in the initiation of allergic disease, many important questions remain to be answered regarding the mechanisms disrupting the normal barrier function. Although our external environment (proteases, allergens, injury) is classically thought of as a principal contributor to barrier disruption associated with allergic sensitization, there is a need to better understand contributions of the internal environment (hormones, diet, circadian clock). Systemic drivers of disease, such as alterations of the endocrine system, metabolism and aberrant control of developmental signaling, are emerging as new players in driving epithelial dysfunction and allergic predisposition at various barrier sites. Identifying such central mediators of epithelial dysfunction, using both systems biology tools and causality-driven laboratory experimentation, will be essential in building new strategic interventions to prevent or reverse the process of barrier loss in allergy.

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Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice

Cited by 42 publications

References 44 publications

Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years

Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years

Vitamin D Insufficiency and Asthma in a US Nationwide Study

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

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