Dataset Information

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat.

ABSTRACT:

Background

Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.

Methods

An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.

Results

Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.

Conclusions

These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.

SUBMITTER: Xu XF

PROVIDER: S-EPMC4233040 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat.

Xu Xue-Feng XF Hu Qiong-Yao QY Liang Ling-Fang LF Wu Lei L Gu Wei-Zhong WZ Tang Li-Li LL Fu Lin-Chen LC Du Li-Zhong LZ

Respiratory research 20141113

<h4>Background</h4>Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.<h4>Methods</h4>An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenet ...[more]

PMID: 25391516

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Project description:IntroductionCeramide is the central substrate of sphingolipid metabolism and plays a key role in cellular signal transduction pathways, regulating apoptosis, differentiation, and chemotaxis. Alterations in airway ceramide levels are observed in multiple pulmonary diseases and recent human genetic association studies have linked dysregulation of sphingolipid regulatory genes with asthma pathogenesis.MethodsUtilizing myriocin, a potent inhibitor of sphingolipid synthesis, we evaluated the immune regulatory role of de novo ceramide generation in vitro and in vivo. Intratracheal myriocin was administered alone or during house dust mite sensitization (HDM) of BALB/C mice and airway hyper-responsiveness (AHR) was evaluated by invasive plethysmography followed by bronchial lavage (BAL) cytology and cytokine quantification.ResultsMyriocin inhibits and HDM exposure activates de novo ceramide synthesis in bone marrow-derived dendritic cells. Mice receiving intratracheal myriocin developed a mild airway neutrophilic infiltrate without inducing a significant increase in AHR. CXCL1 was elevated in the BAL fluid of myriocin-treated mice while the neutrophilic chemotactic factors anaphylatoxin C5a, leukotriene B4, and IL-17 were unaffected. HDM treatment combined with myriocin led to a dramatic enhancement of AHR (63% increase over HDM alone, p < 0.001) and increased granulocyte pulmonary infiltrates versus HDM or myriocin alone. Elevated Th2 T cell counts and Th2 cytokines/chemokines (IL5, IL13, CCL17) were observed in mice treated with combined HDM/myriocin compared to HDM alone. Myriocin-treated pulmonary CD11c+ cells stimulated with HDM secreted significantly more CXCL1 than cells stimulated with HDM alone while HDM stimulated airway epithelial cells showed no change in CXCL1 secretion following myriocin treatment.ConclusionsIntratracheal myriocin, likely acting via ceramide synthesis inhibition, enhances allergen-induced airway inflammation, granulocyte and Th2 lymphocyte recruitment, and allergen-induced AHR. Sphingolipid pathways may represent novel targets for possible future anti-inflammatory asthma medications.

Dataset Information

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat.

Background

Methods

Results

Conclusions

Publications

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat.

Similar Datasets

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