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Lack of involvement of type 7 phosphodiesterase in an experimental model of asthma

E Chevalier1, V Lagente, M Dupont

  • 1Pfizer Global Research and Development, Biology Laboratories, Fresnes, UK.

The European Respiratory Journal
|November 18, 2011
PubMed

Insights

Deleting the phosphodiesterase (PDE)7B gene or inhibiting PDE7A/B did not impact asthma models. These findings suggest PDE7 enzymes are not involved in this allergic asthma model.

Area of Science:

  • Immunology
  • Pharmacology
  • Respiratory Medicine

Background:

  • Type 7 phosphodiesterases (PDE7) reduce intracellular cyclic AMP (cAMP), impacting immune cell function in asthma.
  • Elevating cAMP shows immunosuppressive and anti-inflammatory potential for asthma treatment.

Purpose of the Study:

  • To assess the effect of PDE7B gene deletion on a murine asthma model.
  • To evaluate the efficacy of a selective PDE7A and -B inhibitor in an ovalbumin (OVA)-induced asthma model.

Main Methods:

  • Ovalbumin (OVA)-induced airway inflammation and airway hyperreactivity (AHR) model in mice.
  • Analysis of bronchoalveolar lavage fluid for cell influx and cytokine content.
  • Measurement of AHR and immunoglobulin E (IgE) levels.

Main Results:

  • Neither PDE7B gene deletion nor PDE7A/B inhibition affected airway inflammation or AHR in the OVA model.
  • No significant changes were observed in cytokine levels or IgE serum levels.

Conclusions:

  • PDE7 enzymes do not appear to play a significant role in this specific model of allergic airway inflammation.
  • Targeting PDE7A/B may not be a viable therapeutic strategy for this type of asthma model.

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