Trichostatin A attenuates airway inflammation in mouse asthma model

Authors: J.-H. Choi; S.-W. Oh¹; M.-S. Kang¹; H.J. Kwon²; G.-T. Oh³; D.-Y. Kim¹

Source: Clinical & Experimental Allergy, Volume 35, Number 1, January 2005 , pp. 89-96(8)

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Abstract:

Summary Background

Histone deacetylase (HDAC) inhibition has been demonstrated to change the expression of a restricted set of cellular genes. T cells are essential in the pathogenesis of allergen-induced airway inflammation. It was recently reported that treatment with HDAC inhibitors induces a T cell-suppressive effect. Objective

The purpose of this study was to determine whether treatment with trichostatin A (TSA), a representative HDAC inhibitor, would reduce allergen-induced airway inflammation in a mouse asthma model. Methods

BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and challenged with an aerosol of OVA. TSA (1 mg/kg body weight) was injected intraperitoneally every 2 days beginning on day 1. Mouse lungs were assayed immunohistochemically for HDAC1, a major HDAC subtype, and for infiltration of CD4⁺ cells. The effect of TSA on airway hyper-responsiveness (AHR) was determined, and the bronchoalveolar lavage fluid (BALF) of these mice was assayed for the number and types of inflammatory cells, and for the concentrations of IL-4, IL-5, and IgE. Results

HDAC1 was localized within most airway cells and infiltrating inflammatory cells of asthmatic lungs. Treatment with TSA significantly attenuated AHR, as well as the numbers of eosinophils and lymphocytes in BALF. TSA also reduced infiltration of CD4⁺ and inflammatory cells and mucus occlusions in lung tissue, and decreased the concentrations of IL-4, IL-5, and IgE in BALF. Conclusion

TSA attenuated the development of allergic airway inflammation by decreasing expression of the Th2 cytokines, IL-4 and IL-5, and IgE, which resulted from reduced T cell infiltration. Our results suggest that HDAC inhibition may attenuate the development of asthma by a T cell suppressive effect.

Keywords: allergic airway inflammation; asthma; histone deacetylase; mouse; T lymphocyte; trichostatin A

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2222.2004.02006.x

Affiliations: 1: Department of Veterinary Pathology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul, Korea, 2: Department of Bioscience and Biotechnology, Sejong University, Seoul, Korea and 3: Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea

Publication date: 2005-01-01

Trichostatin A attenuates airway inflammation in mouse asthma model

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