Glucocorticoid Genes and the Developmental Origins of Asthma Susceptibility and Treatment Response

Sharma, Sunita; Kho, Alvin T.; Chhabra, Divya; Qiu, Weiliang; Gaedigk, Roger; Vyhlidal, Carrie A.; Leeder, J. Steven; Barraza‐Villarreal, Albino; London, Stephanie J.; Gilliland, Frank D.; Raby, Benjamin A.; Weiss, Scott T.; Tantisira, Kelan G.

doi:10.1165/rcmb.2014-0109oc

Cited by 22 publications

(20 citation statements)

References 46 publications

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“…The resulting pro-inflammatory environment can result in intrauterine growth restriction (IUGR), a condition associated with fetal hypoxemia, hypoglycemia, and increased catecholamine and cortisol concentrations. High cortisol levels may alter the transcription of GR-regulated genes, which –together with IUGR- could affect lung development [9] [71]. Elevated fetal cortisol is also inversely related to surfactant protein A and B mRNA expression [72], potentially leading to structural lung changes that predispose to post-natal asthma, particularly in neonates with an atopic predisposition (either through heredity or an altered HPA axis).…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

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Prenatal Stress, Prematurity, and Asthma

Medsker¹,

Forno²,

Simhan³

et al. 2015

Obstetrical &Amp; Gynecological Survey

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Asthma is the most common chronic disease of childhood, affecting millions of children in the U.S. and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic Blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced “premature asthma”. Prenatal stress may not only cause abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring Th2 (allergic) immune responses characteristic of atopic asthma: IL-6, which has been associated with premature labor, can promote Th2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing “premature asthma”. If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common co-morbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (e.g. from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health.

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Section: Discussion and Future Directionsmentioning

confidence: 99%

“…Moreover, glucocorticoid-regulated genes are key to fetal lung development, especially during the first and second trimester of pregnancy [9]. In this hypothesis-generating review, we will discuss some potential mechanisms of stress-related asthma in premature children.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Stress, Prematurity, and Asthma

Medsker¹,

Forno²,

Simhan³

et al. 2015

Obstetrical &Amp; Gynecological Survey

View full text Add to dashboard Cite

show abstract

“…A central role of C/EBP-α in the development and maturation of the embryonic lung has been reported by others [68][69][70]. C/EBP-α is also important for the response to the most frequently prescribed antiinflammatory asthma drugs-steroids.…”

Section: Epigenetic Programming Of Cell Function On the Level Of Tranmentioning

confidence: 80%

The Role of Mnk-1, Eukaryotic Translation Initiation Factors and Translation Control in the Pathogenesis of Asthma

Khan¹,

Roth²

2017

J Cell Signal

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“…The response to GCs varies considerably among patients with asthma [33]. Consistent differential expression of CCAAT/enhancer binding protein δ (CEBPD) and DNA-damage inducible transcript 4 (DDIT4) in asthmatics has been reported, suggesting that GC genes, whose changes in expression characterize the response to GCs, are associated with the developmental origins of asthma and treatment response [34].…”

Section: Mechanisms Involved In Gc Resistancementioning

confidence: 98%

Recent Topics in Steroid and Asthma: Beyond the 'Classic' Concept of Action

Matsumura¹

2015

Glob J Allergy

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SummaryGlucocorticoid (GC)s exert anti-inflammatory effects via binding to the glucocorticoid receptor (GR) (NR3C1), targeted gene expression, and protein synthesis, which need hours before the onset of the action (transactivation). GCs also suppress inflammation by direct or indirect interaction with transcription factors, such as activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) (transrepression). Recently, the non-genomic actions of GCs were discovered on recognition of its rapid onset of action within seconds to minutes.GCs target many cells and tissues, including immune and inflammatory cells, airway epithelium, and airway smooth muscle (ASM). Of these, ASM is involved in altered airway contractility. A recent study demonstrated that GCs not only suppress inflammation but also exert direct effects on ASM gene expression which influence ASM function.GC resistance in the treatment of bronchial asthma remains a considerable clinical problem. Genes and cellular inflammatory phenotypes of glucocorticoid-resistant (GC-R) asthma have been revealed. Inflammation-associated protein kinase signaling and transcription factors affect GC actions through modulating GR function. Involvement of chromatin modifications have also been reported. Infection, reduced Vitamin D (Vit D), smoking, and obesity are preventable risk factors in GC-R asthma.Some of these recently available results are presented in this review.

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Glucocorticoid Genes and the Developmental Origins of Asthma Susceptibility and Treatment Response

Cited by 22 publications

References 46 publications

Prenatal Stress, Prematurity, and Asthma

Prenatal Stress, Prematurity, and Asthma

The Role of Mnk-1, Eukaryotic Translation Initiation Factors and Translation Control in the Pathogenesis of Asthma

Recent Topics in Steroid and Asthma: Beyond the 'Classic' Concept of Action

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