title: Lack of involvement of type 7 phosphodiesterase in an experimental model of asthma.
abstract: 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.
authors.affiliation: Pfizer Global Research and Development, Biology Laboratories, Fresnes, UK.
authors.forename: E
authors.initials: E
authors.lastname: Chevalier
authors.forename: V
authors.initials: V
authors.lastname: Lagente
authors.forename: M
authors.initials: M
authors.lastname: Dupont
authors.forename: H
authors.initials: H
authors.lastname: Fargeau
authors.forename: X
authors.initials: X
authors.lastname: Palazzi
authors.forename: V
authors.initials: V
authors.lastname: Richard
authors.forename: M
authors.initials: M
authors.lastname: Dassaud
authors.forename: M
authors.initials: M
authors.lastname: Fric
authors.forename: M
authors.initials: M
authors.lastname: Coupe
authors.forename: C
authors.initials: C
authors.lastname: Carré
authors.forename: S
authors.initials: S
authors.lastname: Leduc
authors.forename: P
authors.initials: P
authors.lastname: Bernardelli
authors.forename: F
authors.initials: F
authors.lastname: Vergne
authors.forename: P
authors.initials: P
authors.lastname: Berna
authors.forename: C P
authors.initials: CP
authors.lastname: Bertrand
mesh_terms: D000631:Aminopyridines / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D001549:Benzamides / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors / Q000235:genetics*; D003521:Cyclopropanes / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D016207:Cytokines; C424423:Roflumilast; D007073:Immunoglobulin E; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517459:Pde7a protein, mouse; C517465:Pde7b protein, mouse