IL-4 amplifies the pro-inflammatory effect of adenosine in human mast cells by changing expression levels of adenosine receptors.
IL-4 amplifies the pro-inflammatory effect of adenosine in human mast cells by changing expression levels of adenosine receptors.
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DOI：
10.1371/journal.pone.0024947
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tilley SL
中科院分区：
文献类型：
--
作者：
Hua X;Chason KD;Patel JY;Naselsky WC;Tilley SL
吸入腺苷可使哮喘患者立即产生支气管收缩，但对正常人无此作用。腺苷的支气管痉挛作用主要是通过腺苷诱导的肥大细胞活化介导的，由于在培养人原代肥大细胞方面的限制，其机制知之甚少。在这里，我们表明，人脐带血来源的肥大细胞与Th 2细胞因子IL-4孵育开发增加的敏感性腺苷。增强抗IgE诱导的和钙离子载体/PMA诱导的脱粒与IL-4培养的肥大细胞，这种效果被减少或取消预处理A2 BsiRNA和选择性A2 B受体拮抗剂，分别。IL-4孵育导致人肥大细胞上A2 B腺苷受体的表达增加和A2 A腺苷受体的表达减少。这些结果表明，哮喘肺中的Th 2细胞因子可能改变气道肥大细胞上腺苷受体的表达，以促进对腺苷的反应性增加。
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 A2BsiRNA and selective A2B receptor antagonists, respectively. IL-4 incubation resulted in the increased expression of A2B and reduced expression of A2A 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.