RT Journal Article
SR Electronic
T1 Lack of involvement of type 7 phosphodiesterase in an experimental model of asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 582
OP 588
DO 10.1183/09031936.00102610
VO 39
IS 3
A1 E. Chevalier
A1 V. Lagente
A1 M. Dupont
A1 H. Fargeau
A1 X. Palazzi
A1 V. Richard
A1 M. Dassaud
A1 M. Fric
A1 M. Coupe
A1 C. Carré
A1 S. Leduc
A1 P. Bernardelli
A1 F. Vergne
A1 P. Berna
A1 C.P. Bertrand
YR 2012
UL http://erj.ersjournals.com/content/39/3/582.abstract
AB Type 7 phosphodiesterases (PDE7) are responsible for the decrease of intracellular cyclic AMP (cAMP) in many cells involved in allergic asthma by suppressing their potential to respond to many activating stimuli. The elevation of intracellular cAMP has been associated with immunosuppressive and anti-inflammatory activities and represents a potential treatment of asthma. Our aim was to evaluate the impact of the deletion of the murine phosphodiesterase (PDE)7B gene and then to evaluate the efficacy of a newly described selective PDE7A and -B inhibitor on an ovalbumin (OVA)-induced airway inflammation and airway hyperreactivity (AHR) model in mice. Inflammation was determined 72 h after single OVA challenge or 24 h after multiple challenges by the relative cell influx and cytokine content in bronchoalveolar lavage fluid. AHR and immunoglobulin E levels in serum were determined after multiple challenges. For the first time, we have demonstrated that the deletion of the PDE7B gene or the pharmacological inhibition of PDE7A and -B had no effect on all the parameters looked at in this model. These results highlight the absence of any implication of the PDE7 enzyme in our model.