Performance evaluation of histone deacetylases in lungs of mice exposed to ovalbumin aerosols.

This study was to investigate expression levels and functional activities of histone deacetylases (HDACs) with potential therapeutic targets selected in animal model of allergic asthma. Mice were sensitized and then challenged with saline (control) or ovalbumin (OVA) for 8 weeks. Airway resistance was determined by increasing concentrations of acetyl-β-methacholine chloride (0 - 50 mg/ml). The number of cells and cytokine production in bronchoalveolar lavage fluid (BALF) were determined by ELISA. Pathological changes of lung specimens were examined by histochemical staining methods under the light microscope. Expression and quantification of HDACs in lungs were measured using immunohistochemistry and Western blotting analysis. HDAC activity was identified using colorimetric and fluorometric methods. The OVA-treated mice had a significant enhancement in airway resistance with a large number of cells and increased interleukin (IL)-4 and -5 levels in BALF. Morphologically, an infiltration of inflammatory cells into epithelial layer with mucus accumulation and subepithelial fibrosis were seen in the OVA-exposed lungs. The expression levels for HDAC1, HDAC5, HDAC6, and HDAC8 were significantly elevated with weak induction of HDAC 2-4, which was identical with their catalytic activities detected in the lungs. In contrast, HDAC1 and HDAC5 activities were higher than others in the lungs. Individual HDACs are differently regulated in expression levels and functional activities in animal model of allergic asthma. Selective targeting of HDAC1/5 offers an opportunity to improve therapeutic effects of the disease.