P2Y6 receptor activation improves lung function, immunology, and structure in asthmatic mice

What is it about?

Control of severe asthma remains a major problem. This study evaluate the ability of purinergic P2Y6 activation to ameliorate asthma pathology in a mouse allergic asthma model. The pro-drug GC021109, which metabolizes into a P2Y6 receptor activator, was administered to mice simultaneously with allergen provocation of house dust mitogen daily for 6 weeks. Pulmonary function testing showed dose-dependent normalization of airway resistance and compliance. Immune cytokines were reduced to near-normal or normal levels in a dose-dependent manner. Airway smooth muscle hypertrophy was reduced to normal. The study provides evidence that P2Y6 receptor activity can reduce inflammatory responses and improve lung function in this allergic asthma model.

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Why is it important?

Controlling severe asthma is a major medical problem. The role of P2Y6 receptors in the pathogenesis of severe asthma is controversial. Some studies indicate these receptors may activate inflammatory processes in the airway; other studies suggest the receptors may ameliorate asthmatic responses. This study demonstrates the ability of a P2Y6 agonist pro-drug to significantly modify allergic asthma pathology when given over a chronic interval of time. This suggests a novel therapeutic approach to severe asthma.