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.

Role of Phosphodiesterase 7 (PDE7) in T Cell Activity. Effects of Selective PDE7 Inhibitors and Dual PDE4/7 Inhibitors on T Cell Functions

“…No inhibition in T lymphocyte proliferation or cytokine production by Th1 and Th2 cells after CD3/CD28 co-stimulation was observed. A similar conclusion resulted from a study conducted by Chevalier et al [51], who reported that PDE7 was not involved in an experimental model of asthma in ovalbumin-immunized mice. A deletion of the PDE7B gene in knockout mice had no effect on the following tested parameters: airway hyperreactivity, cytokine levels in bronchoalveolar lavage, inflammatory cell infiltration, and total IgE in serum.…”

“…Regarding respiratory diseases, PDE7 inhibitors may have beneficial effects in asthma and COPD due to relaxation of airway smooth muscles and anti-inflammatory properties [67,68], as well as in smoke-induced lung inflammation in mice [69]. However, Chevalier et al [51] showed no effects of PDE7 inhibition in an experimental model of asthma in mice. Some studies demonstrated that PDE7 inhibitors, PDE4/7 inhibitor or a combination of PDE3, 4, and 7 inhibitors induced apoptosis of leukemic cells [45,46,70].…”

Deducting MicroRNA-Mediated Changes Common in Bronchial Epithelial Cells of Asthma and Chronic Obstructive Pulmonary Disease—A Next-Generation Sequencing-Guided Bioinformatic Approach

“…Since PDE7 involved in T cell activation, PDE7 had been considered as a potential therapeutic target for chronic inflammatory diseases including asthma and COPD [46,47,48]. However, a study showed no involvement of PDE7A and PDE7B in the asthmatic mice model of ovalbumin-induced airway inflammation and hyper-reactivity [49]. To the best of our knowledge, no literature has reported the suppressive effect of miR-10a-5p or miR-146a-5p on PDE7A .…”

Exploration of the Molecular Mechanism of FUZI (Aconiti Lateralis Radix Praeparata) in Allergic Rhinitis Treatment Based on Network Pharmacology

“…It has been reported that activation of the cAMP/PKA signaling pathway in mast cells can mitigate its degranulation and inhibit allergic reaction [45]. Elevated cAMP levels can exert immunosuppressive and antiinflammatory effects in cells, which is a potential treatment for autoimmune diseases [46]. Phosphodiesterase 4 (PDE4) refers to an enzyme degrading cAMP.…”