Phosphodiesterases Inhibition by Bacilli Calmette-Guérin Contributes to Decrease Asthma in Allergic Rats

Phosphodiesterases  (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-Guérin (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 sensitized 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.