ArticleAmerican journal of respiratory cell and molecular biology2012
Trichostatin A abrogates airway constriction, but not inflammation, in murine and human asthma models.
Article in American journal of respiratory cell and molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 84 citations in OpenAlex.
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- Toll-Interacting Protein Down-Regulation by Cigarette Smoke Exposure Impairs Human Lung Defense against Influenza A Virus Infection.The American journal of pathology · 2025Article
- Review
- Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells.Clinical epigenetics · 2023Article
- Innovative three-dimensional models for understanding mechanisms underlying lung diseases: powerful tools for translational research.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Inhaled drug delivery for the targeted treatment of asthma.Advanced drug delivery reviews · 2023Review
- Functional changes in long-term incubated rat precision-cut lung slices.Respiratory research · 2022Article
- Cellular sources of airway smooth muscle cells in asthmatic airway remodeling and their clinical relevance: a narrative review.Annals of translational medicine · 2022Article
- RAGE mediates airway inflammation via the HDAC1 pathway in a toluene diisocyanate-induced murine asthma model.BMC pulmonary medicine · 2022Article
- The Challenge of Long-Term Cultivation of Human Precision-Cut Lung Slices.The American journal of pathology · 2022Article
- Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.Pharmaceutics · 2022Review
- Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance.Frontiers in cell and developmental biology · 2022Review
- Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.American journal of respiratory cell and molecular biology · 2021Review
- Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use.The European respiratory journal · 2021Article
- Preclinical and clinical progress for HDAC as a putative target for epigenetic remodeling and functionality of immune cells.International journal of biological sciences · 2021Review
- Investigation of molecular mechanisms of experimental compounds in murine models of chronic allergic airways disease using synchrotron Fourier-transform infrared microspectroscopy.Scientific reports · 2020Article
- Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid.The Journal of biological chemistry · 2020Article
- Proteomics profiling asthma induced-lysine acetylation.EXCLI journal · 2020Article
- Use of precision cut lung slices as a translational model for the study of lung biology.Respiratory research · 2019Review
- Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis.Respiratory research · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Histone deacetylase (HDAC) inhibitors may offer novel approaches in the treatment of asthma. We postulate that trichostatin A (TSA), a Class 1 and 2 inhibitor of HDAC, inhibits airway hyperresponsiveness in antigen-challenged mice. Mice were sensitized and challenged with Aspergillus fumigatus antigen (AF) and treated with TSA, dexamethasone, or vehicle. Lung resistance (R(L)) and dynamic compliance were measured, and bronchial alveolar lavage fluid (BALF) was analyzed for numbers of leukocytes and concentrations of cytokines. Human precision-cut lung slices (PCLS) were treated with TSA and their agonist-induced bronchoconstriction was measured, and TSA-treated human airway smooth muscle (ASM) cells were evaluated for the agonist-induced activation of Rho and intracellular release of Ca(2+). The activity of HDAC in murine lungs was enhanced by antigen and abrogated by TSA. TSA also inhibited methacholine (Mch)-induced increases in R(L) and decreases in dynamic compliance in naive control mice and in AF-sensitized and -challenged mice. Total cell counts, concentrations of IL-4, and numbers of eosinophils in BALF were unchanged in mice treated with TSA or vehicle, whereas dexamethasone inhibited the numbers of eosinophils in BALF and concentrations of IL-4. TSA inhibited the carbachol-induced contraction of PCLS. Treatment with TSA inhibited the intracellular release of Ca(2+) in ASM cells in response to histamine, without affecting the activation of Rho. The inhibition of HDAC abrogates airway hyperresponsiveness to Mch in both naive and antigen-challenged mice. TSA inhibits the agonist-induced contraction of PCLS and mobilization of Ca(2+) in ASM cells. Thus, HDAC inhibitors demonstrate a mechanism of action distinct from that of anti-inflammatory agents such as steroids, and represent a promising therapeutic agent for airway disease.
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