P2Y(6) contributes to ovalbumin-induced allergic asthma by enhancing mast cell function in mice

Extracelluar nucleotides have been identified as regulatory factors in asthmatic pathogenesis by activating purinergic receptors. This research aimed to investigate the function of the purinergic receptor P2Y(6) in mediating airway inflammation in allergic asthma. Wild-type (WT) and P2Y(6)-deficient mice were stimulated with ovalbumin (OVA) to construct asthmatic mouse models. Overexpression of P2Y(6) and uridine 5′-diphosphate (UDP)-releasing were demonstrated in lung tissues in ovalbumin-induced asthmatic mice. The release of the cytokine IL-4, mast cell invasion, and the airway remodeling phenotypes were more severe following the application of UDP in asthmatic mice. However, P2Y(6) deficiency reduced these asthmatic pathogeneticsymptoms markedly in a mouse model. In vitro, we found that P2Y(6) in purified mast cells enhanced the functions of mast cells in the inflammatory response in the asthmatic process by triggering their capability for migration, cytokine secretion and granule release. Moreover, P2Y(6) stimulated the function of mast cells through activation of the AKT signaling pathway. Our data provides evidence that P2Y(6) contributes to allergic airway inflammation and remodeling by enhancing the functions of mast cells in ovalbumin-induced asthmatic mice.