Abstract
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 P2Y6 in mediating airway inflammation in allergic asthma. Wild-type (WT) and P2Y6-deficient mice were stimulated with ovalbumin (OVA) to construct asthmatic mouse models. Overexpression of P2Y6 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, P2Y6 deficiency reduced these asthmatic pathogeneticsymptoms markedly in a mouse model. In vitro, we found that P2Y6 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, P2Y6 stimulated the function of mast cells through activation of the AKT signaling pathway. Our data provides evidence that P2Y6 contributes to allergic airway inflammation and remodeling by enhancing the functions of mast cells in ovalbumin-induced asthmatic mice.
Highlights
Asthma is a kind of chronic lung disease characterized by airway inflammation, remodeling, and hyperresponsiveness [1,2,3]
The enzyme-linked immunosorbent assay (ELISA) results showed that the levels of IL-4 and IL-5 in bronchioalveolar lavage fluid (BALF) were increased on the 21st day after stimulation with 100 μg ovalbumin (Figure 1B)
The results proved that the release of uridine 5’-diphosphate (UDP) was accompanied by alteration of expression of P2Y6 (Figure 1F)
Summary
Asthma is a kind of chronic lung disease characterized by airway inflammation, remodeling, and hyperresponsiveness [1,2,3]. Asthma is derived from sensitization via the airways to some common sensibiligen [4, 5]. They will cause airway inflammation through the release of inflammatory mediators, which is assumed to be the initiating event of airway remodeling. In allergic airway inflammation, including the innate and adaptive immune responses, eosinophils, macrophages, T helper type 2 (Th2) cells, and mast cells are involved in the inflammatory response of asthma [3, 6, 7]. Mast cells play key roles in the allergic inflammation response, airway remodeling and symptomatology [8]. The mechanism of function of mast cells in asthma is being actively studied
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