| Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease. | |
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MedLine Citation:
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PMID: 22139576 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Airway remodeling and airway hyperresponsiveness are major aspects of asthma pathology that are not targeted optimally by existing anti-inflammatory drugs. Histone deacetylase inhibitors have a wide range of effects that may potentially abrogate aspects of remodeling. One such histone deacetylase inhibitor is valproic acid (2-propylvaleric acid). Valproic acid is used clinically as an anti-epileptic drug and is a potent inhibitor of class I histone deacetylases but also inhibits class II histone deacetylases. We used valproic acid as a molecular model of histone deacetylase inhibition in vivo in chronic allergic airways disease mice with airway remodeling and airway hyperresponsiveness. Wild-type Balb/c mice with allergic airways disease were treated with valproic acid or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and examination of lung tissue sections. Remodeling was assessed by morphometric analysis of histochemically stained slides and lung function was assessed by invasive plethysmography measurement of airway resistance. Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0.01), reduced subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness (p < 0.05 and p < 0.01 for the two highest doses of methacholine, respectively). These findings show that treatment with valproic acid can reduce structural airway remodeling changes and hyperresponsiveness, providing further evidence for the potential use of histone deacetylase inhibitors for the treatment of asthma. |
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Authors:
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Simon G Royce; William Dang; Katherine Ververis; Nishika De Sampayo; Assam El-Osta; Mimi L K Tang; Tom C Karagiannis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Epigenetics : official journal of the DNA Methylation Society Volume: 6 ISSN: 1559-2308 ISO Abbreviation: Epigenetics Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-05 Completed Date: 2012-04-02 Revised Date: 2012-04-13 |
Medline Journal Info:
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Nlm Unique ID: 101265293 Medline TA: Epigenetics Country: United States |
Other Details:
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Languages: eng Pagination: 1463-70 Citation Subset: IM |
Affiliation:
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Allergy and Immune Disorders, Murdoch Children's Research Institute, Parkville VIC, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Airway Remodeling
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drug effects* Animals Asthma / drug therapy*, pathology, physiopathology Bronchial Hyperreactivity / drug therapy, pathology* Bronchoalveolar Lavage Fluid / cytology Disease Models, Animal Female Histone Deacetylase Inhibitors / therapeutic use* Humans Inflammation / drug therapy, pathology Mice Mice, Inbred BALB C Valproic Acid / therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/Histone Deacetylase Inhibitors; 99-66-1/Valproic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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