Abstract
Histamine H1 receptor antagonists are useful in the treatment of allergic diseases. Recent in vitro experimental studies suggest that H1 receptor antagonists produce their anti-inflammatory effects by inhibition of basal nuclear factor (NF) -κB activity. In the present study, we investigated the effects of ebastine on gene expression, airway inflammation, and goblet cell metaplasia in a murine model of asthma. Groups of mice were sensitized with two intraperitoneal injections of ovalbumin (OVA) on Days 0 and 7. Mice were then challenged intranasally with OVA on Days 24-26 during a course of treatment with either phosphate-buffered saline or ebastine on Days 21-27. After OVA challenge, bronchoalveolar lavage fluid (BALF) and lung tissue specimens were collected. BALF was analyzed for differential cell counts, whereas lung tissue was examined for NF-κB activity and the gene expression of cytokines, chemokines, GATA3, and muc5ac. Lung tissues were stained with periodic acid-Schiff. Airway eosinophilia, increased NF-κB activity, and increased gene expression in the lung of cytokines [interleukin (IL) -4, IL-5, interferon-γ, and tumor necrosis factor-α], chemokines (CCL11, CCL17, and CXCL10), and GATA3 were observed in OVA-sensitized and -challenged mice. These increases were significantly inhibited by ebastine treatment. Moreover, mucus occlusion was significantly inhibited in ebastine-treated mice, with a decrease in muc5ac gene expression compared with untreated mice. These results indicate that ebastine prevents airway inflammation and goblet cell metaplasia in a murine model of asthma partly by inhibiting NF-κB activity and the expression of GATA3.
