Trichostatin A attenuates airway inflammation in mouse asthma model.
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.


CONCLUSIONS
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.
Choi
J-H
JH
Department of Veterinary Pathology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
Oh
S-W
SW
Kang
M-S
MS
Kwon
H J
HJ
Oh
G-T
GT
Kim
D-Y
DY
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000032:analysis; D007150:Immunohistochemistry / Q000379:methods; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; C012589:trichostatin A; D010047:Ovalbumin