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IL-4 Amplifies the Pro-Inflammatory Effect of Adenosine in Human Mast Cells by Changing Expression Levels of Adenosine Receptors
Journal article   Open access   Peer reviewed

IL-4 Amplifies the Pro-Inflammatory Effect of Adenosine in Human Mast Cells by Changing Expression Levels of Adenosine Receptors

Xiaoyang Hua, Kelly D. Chason, Janki Y. Patel, Warren C. Naselsky and Stephen L. Tilley
PloS one, Vol.6(9), pp.e24947-e24947
09/26/2011
DOI: 10.1371/journal.pone.0024947
PMCID: PMC3180290
PMID: 21966389
url
https://doi.org/10.1371/journal.pone.0024947View
Published (Version of record) Open Access

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.
Biology Medicine

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