A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury
A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury
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DOI：
10.1172/jci200522656
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发表时间：
2005-01-01
影响因子：
15.9
通讯作者：
Blackburn, MR
中科院分区：
文献类型：
--
作者：
Sun, CX;Young, HW;Blackburn, MR
腺苷是一种信号核苷，参与哮喘和慢性阻塞性肺病的调节。腺苷信号传导可以在组织和细胞中起到促炎和抗炎作用。在这项研究中，我们研究了腺苷受体（A（1）AR）信号传导对腺苷脱氨酶缺陷（ADA缺陷）小鼠肺炎症和损伤的作用，这些小鼠表现出腺苷水平升高。实验表明，ADA缺陷小鼠肺中A（1）AR的转录水平升高，其表达主要定位于肺泡巨噬细胞。从ADA缺陷小鼠中遗传性去除A（1）AR导致肺部炎症增强沿着粘液化生和肺泡破坏增加。这些变化与Th 2细胞因子IL-4和IL-13在肺中的过度表达以及趋化因子和基质金属蛋白酶的表达增加有关。这些发现表明，A（1）AR在ADA缺陷小鼠的肺表型中发挥抗炎和/或保护作用，这表明A（1）AR信号可能通过控制肺部炎症和损伤的重要介质水平来调节慢性肺部疾病中肺部炎症和重塑的严重程度。
Adenosine is a signaling nucleoside that has been implicated in the regulation of asthma and chronic obstructive pulmonary disease. Adenosine signaling can serve both pro- and anti-inflammatory functions in tissues and cells. In this study we examined the contribution of A(1) adenosine receptor (A(1)AR) signaling to the pulmonary inflammation and injury seen in adenosine deaminase-deficient (ADA-deficient) mice, which exhibit elevated adenosine levels. Experiments revealed that transcript levels for the A(1)AR were elevated in the lungs of ADA-deficient mice, in which expression was localized predominantly to alveolar macrophages. Genetic removal of the A(1)AR from ADA-deficient mice resulted in enhanced pulmonary inflammation along with increased mucus metaplasia and alveolar destruction. These changes were associated with the exaggerated expression of the Th2 cytokines IL-4 and IL-13 in the lungs, together with increased expression of chemokines and matrix metalloproteinases. These findings demonstrate that the A(1)AR plays an anti-inflammatory and/or protective role in the pulmonary phenotype seen in ADA-deficient mice, which suggests that A(1)AR signaling may serve to regulate the severity of pulmonary inflammation and remodeling seen in chronic lung diseases by controlling the levels of important mediators of pulmonary inflammation and damage.