Asthma is an allergic inflammatory disease of the lungs characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). Exposure to environmental endotoxins, such as lipopolysaccharide (LPS), can exacerbate asthma severity. Phosphodiesterase (PDE) inactivates cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate, thereby aggravating inflammation. Accordingly, PDE inhibitors could be used to treat asthma. Herein, we studied the effects of BRL-50481 (BRL), a PDE7 inhibitor, in a murine model of ovalbumin (OVA)-induced allergic asthma with co-exposure to LPS. Mice were sensitized, challenged with OVA, and subsequently exposed to LPS. Mice were administered with BRL prior to the OVA challenge. We observed that BRL treatment could suppress hallmark features of asthma, including mediators of eosinophilic and neutrophilic inflammation, such as expression of antigen-specific immunoglobulin (Ig) E, interleukin (IL)-13, IL-6, and mucus hypersecretion. Mice co-exposed to OVA and LPS exhibited marked AHR, which was improved in BRL-treated mice because of inhibition of mucus overproduction. In conclusion, given that PDE7 inhibitors can regulate allergic inflammatory responses, these agents could be potential candidates for treating asthma.
Keywords: Asthma; BRL-50481; Lipopolysaccharide; Phosphodiesterase.