Carboxyamidotriazole ameliorates inflammation in experimental allergic asthma by inhibiting the expression of phosphodiesterase 4

Abstract

Abstract Objective Carboxyamidotriazole (CAI) is a small molecular drug with anti-inflammatory and anti-tumor effects, which can inhibit a variety of phosphodiesterases (PDEs) isolated from multiple tissue sources. The present study aims to explore the effect of CAI on allergic asthma of experimental mice model, and further verify the relation between CAI and specific PDE. Methods An in vitro model of lipopolysaccharide (LPS) stimulated-rat alveolar macrophages NR8383 and an in vivo model of ovalbumin (OVA) sensitized mice were used to examine the anti-inflammation effect of CAI. Airway hyperresponsiveness (AHR) was measured by Forced Maneuvers Pulmonary Function Testing (BUXCO). Fixative lung tissue was stained to observe the airway remodelling and the mucous secretion. mRNA expression of PDE-4A/B/D were detected by RT-qPCR. Key findings: In rat alveolar macrophage NR8383, CAI significantly reduced the inflammation induced by LPS and restrained the expression of PDE-4B. In mice with allergic airway inflammation, CAI can effectively reduce airway hyperresponsiveness, inhibit inflammatory factor secretion, alleviate the accumulation of inflammatory cells and reduce the levels of IgE in plasma. Airway remodeling manifested by smooth muscle thickening, cell proliferation, pro-inflammatory cytokines secretion and inflammatory cells gathering around the airway in mice was significantly prevented by CAI. CAI effectively restrained the expression of PDE-4A, PDE-4B and PDE-4D in lung tissue. Conclusion CAI can inhibit inflammatory activities both in activated macrophages and allergic asthma animal models, which might be related to reduction the expression of PDE4.