title: IL-4 amplifies the pro-inflammatory effect of adenosine in human mast cells by changing expression levels of adenosine receptors.
abstract: Adenosine inhalation produces immediate bronchoconstriction in asthmatics but not in normal subjects. The bronchospastic effect of adenosine is largely mediated through adenosine-induced mast cell activation, the mechanism of which is poorly understood due to limitations in culturing human primary mast cells. Here, we show that human umbilical cord blood -derived mast cells incubated with the Th2 cytokine IL-4 develop increased sensitivity to adenosine. Potentiation of anti-IgE- induced and calcium ionophore/PMA-induced degranulation was augmented in mast cells cultured with IL-4, and this effect was reduced or abolished by pre-treatment with A(2B)siRNA and selective A(2B) receptor antagonists, respectively. IL-4 incubation resulted in the increased expression of A(2B) and reduced expression of A(2A) adenosine receptors on human mast cells. These results suggest that Th2 cytokines in the asthmatic lung may alter adenosine receptor expression on airway mast cells to promote increased responsiveness to adenosine.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, and the Center of Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Hua
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Chason
authors.forename: Janki Y
authors.initials: JY
authors.lastname: Patel
authors.forename: Warren C
authors.initials: WC
authors.lastname: Naselsky
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Tilley
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D001771:Blood Banks; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis*; D043704:Receptor, Adenosine A2B / Q000096:biosynthesis*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D053802:Tryptases / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1; D015847:Interleukin-4; D007073:Immunoglobulin E; D006596:Hexosaminidases; D053802:Tryptases; D000241:Adenosine