Inhibition of phosphodiesterase suppresses allergic lung inflammation by regulating MCP-1 in an OVA-induced asthma murine model with co-exposure to lipopolysaccharide.

Abstract

ObjectiveAsthma is a chronic inflammatory disease that can lead to severe problems with the respiratory system. This study aimed to evaluate the suppression of allergic airway inflammation of an asthma murine model by 3-isobutyl-1-methylxanthine (IBMX), which is a non-specific cyclic nucleotide phosphodiesterase (PDE) inhibitor.MethodsAllergic lung inflammation was evoked by ovalbumin (OVA) alone or co-exposure with lipopolysaccharide (LPS) in a murine asthma model.ResultsCompared with the OVA alone-treated control, co-exposure with LPS significantly enhanced allergic inflammatory responses in airway hyperresponsiveness and pathologic changes of the asthmatic mouse lung. Specifically, LPS enhanced allergic asthma through the increase of monocyte chemoattractant protein (MCP)-1 release. However, IBMX significantly suppressed specific airway resistance and tidal volume, the infiltration of eosinophils and mast cells into the lung, the levels of serum immunoglobulin (Ig)E and IgG1, and the release of Th2 cytokines (interleukin (IL)-4, IL-13, and MCP-1). IBMX attenuated the aggravation of inflammation by inhibiting MCP-1, and inhibited the infiltration of eosinophils and the production of Th2 cell-associated inflammatory mediators.ConclusionThese results demonstrate the therapeutic potential of targeting the regulation of PDE activity in an aggravated chronic allergic asthmatic response after bacterial infection.