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Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
The impact of benzo[a]pyrene on murine allergic airway inflammation via epigenetic remodeling
Xihua Wang1, Shuyuan Guan1, Lingbin Sun2
1Department of Anesthesiology, Peking University Shenzhen Hospital, Shenzhen, China.
Abstract:
Simultaneous exposure to both BaP and house dust mites (HDM) has been shown to exacerbate pulmonary inflammation and hyperresponsiveness in a murine asthma model. The mechanistic insight into epigenetic inheritance for this effect, however, remains to be clarified. As such, in this study, we explore the molecular basis for the enhancement of asthma. Female BAL/C mice were intranasally administered HDM (25 µg in 25 μL saline) and/or BaP (10 μg/kg) every other day for 9 weeks. RNA sequencing and DNA methylation assessment were used to explore the underlying mechanism. Following simultaneous exposure to HDM and BaP, mice exhibited pulmonary inflammation and the transcript level of IL4i1b, muc4 and IL22ra2 that were associated with altered DNA methylation, suggesting that there may be an epigenetic basis for BaP-induced asthma exacerbation. Our data suggest that DNA methylation is a major epigenetic modification that accompanies airway remodeling associated with changes in the allergic mice.
Insights
Simultaneous exposure to benzo(a)pyrene (BaP) and house dust mites (HDM) worsens asthma in mice. Epigenetic changes, specifically DNA methylation, appear to underlie this exacerbation, impacting airway remodeling.
Area of Science:
- Environmental Health
- Immunology
- Epigenetics
Background:
- Simultaneous exposure to benzo(a)pyrene (BaP) and house dust mites (HDM) exacerbates pulmonary inflammation and hyperresponsiveness in murine asthma models.
- The precise mechanistic insights, particularly regarding epigenetic inheritance, require further clarification.
Purpose of the Study:
- To explore the molecular basis for BaP-induced enhancement of asthma when co-exposed with HDM.
- To investigate the role of epigenetic modifications in BaP and HDM-mediated asthma exacerbation.
Main Methods:
- Female BAL/C mice were intranasally administered HDM and/or BaP every other day for 9 weeks.
- RNA sequencing and DNA methylation assessments were employed to elucidate the underlying mechanisms.
- Analysis of transcript levels for IL4i1b, muc4, and IL22ra2 in conjunction with DNA methylation patterns.
Main Results:
- Simultaneous HDM and BaP exposure led to significant pulmonary inflammation in mice.
- Altered DNA methylation patterns were observed, correlating with changes in the transcript levels of IL4i1b, muc4, and IL22ra2.
- These findings suggest an epigenetic basis for BaP-induced asthma exacerbation.
Conclusions:
- DNA methylation is a key epigenetic modification involved in airway remodeling in allergic mice exposed to BaP and HDM.
- Epigenetic mechanisms contribute to the exacerbation of asthma symptoms by environmental pollutants like BaP in the presence of allergens.
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