Phosphodiesterases inhibition by bacilli calmette-guerin contributes to decrease asthma in allergic rats

ABSTRACT

Phosphothesterases [PDE] hydrolyse intracellular cAMP and cGMP to inactive 5' monophosphates Decreased level of cAMP is involved in the pathogenesis of asthma. We and others have shown that phosphodiesterases were upregulated in the lung of allergic rats, and Bacilli Calmette-Guerin [BCG] induced the production of cAMP in vitro. However, it is unclear how BCG's effect asthma and whether it is related to PDEs. In this study, BCG was intraperitoneally injected into male Sprague-Dawley rats sensitrized and later the rats were challenged with ovabumin/pertusis. The inflammation in lungs was measured. Airway hyperresponsiveness was determined using MedLab software after intravenous methacholine challenge. Furthermore cAMP level and adenylate cyclase activity in lungs were analyzed by ELISA, Phosphodiesterases activities were analyzed by HPLC, while PDEs mRNA levels in lungs was analyzed by reverse transcription-polymerase chain reaction. Administration of BCG significantly attenuated allergen-induced lung inflammatory response and hyper responsiveness as compared with vehicle treatment. Furthermore, the levels of cAMP in lungs were significantly increased in BCG-treated allergic rats. Interestingly, administration of BCG decreased the activity of cAMP-PDE, but not adenylyl cyclase [AC], activity in lungs of animals. Furthermore, pretreatment with BCG significantly decreased the mRNA levels of PDE4A, 4C, 5 and 8, which were induced in lungs of allergic rats. BCG administration attenuated airway inflammatory response and bronchial hyper responsiveness in rats, which are the most important symptoms in asthma. The decreased PDEs mRNA and inhibited cAMP-PDE activities by BCG contribute, at least in part, prevention of allergen-induced airway inflammation and asthma in rats