title: P2Y6 contributes to ovalbumin-induced allergic asthma by enhancing mast cell function in mice.
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.
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Jue-Ping
authors: JP
authors: Shi
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Shao-Ying
authors: SY
authors: Wang
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Li-Li
authors: LL
authors: Chen
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Xiao-Yu
authors: XY
authors: Zhang
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Yi-Han
authors: YH
authors: Zhao
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Bing
authors: B
authors: Du
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Wen-Zheng
authors: WZ
authors: Jiang
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Min
authors: M
authors: Qian
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R.China.
authors: Hua
authors: H
authors: Ren
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000235:genetics* / Q000378:metabolism; D007073:Immunoglobulin E / Q000737:chemistry; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000378:metabolism*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014530:Uridine Diphosphate
chemical_list: D016207:Cytokines; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D015847:Interleukin-4; D007073:Immunoglobulin E; D014530:Uridine Diphosphate; D010047:Ovalbumin
keywords: Immune response; Immunity; Immunology and Microbiology Section; P2Y6; UDP; asthma; mast cell; migration