Mohsenin Amir, Blackburn Michael R
Department of Biochemistry and Molecular Biology, University of Texas - Houston Medical School, Houston, Texas 77030, USA.
Curr Opin Pulm Med. 2006 Jan;12(1):54-9. doi: 10.1097/01.mcp.0000199002.46038.cb.
The chronic lung diseases, asthma and chronic obstructive pulmonary disease, are pulmonary disorders in which persistent inflammation and alterations in lung structure contribute to a progressive loss of lung function. Although the exact type of inflammation and damage in each disease is distinct, they share the common feature that they are chronic in nature. Despite efforts, little is known about the cellular and molecular mechanisms that drive the chronicity of these two diseases. This review will summarize important findings regarding the role of adenosine, a signaling nucleoside implicated in the pathogenesis of these two disorders.
Aerosolized adenosine induces bronchoconstriction in patients with asthma and chronic obstructive pulmonary disease primarily through the release of mast cell mediators. In this setting it can not only be used to aid in diagnosis but also to monitor patient responses to steroid therapy. Adenosine levels are elevated in the lungs of asthma patients, indicating greater flux through adenosine receptor signaling pathways. In-vitro studies have shown adenosine to access pathways leading to the genesis of chronic inflammation via the release of proinflammatory cytokines and chemokines. Animal studies demonstrate that merely elevating adenosine levels in the mouse is sufficient to induce a pulmonary phenotype with features of asthma and chronic obstructive pulmonary disease.
Identifying mediators regulating the chronic nature of asthma and chronic obstructive pulmonary disease is critical towards advancements in treatment options. Adenosine has been implicated in promoting the inflammation and airway remodeling seen in chronic lung disease and thus makes an attractive therapeutic target.
慢性肺部疾病，如哮喘和慢性阻塞性肺疾病，是肺部疾病，其中持续的炎症和肺结构改变导致肺功能逐渐丧失。尽管每种疾病的确切炎症类型和损伤不同，但它们都有一个共同特点，即本质上是慢性的。尽管人们做出了努力，但对于驱动这两种疾病慢性化的细胞和分子机制知之甚少。本综述将总结关于腺苷作用的重要发现，腺苷是一种参与这两种疾病发病机制的信号核苷。
雾化腺苷主要通过肥大细胞介质的释放，在哮喘和慢性阻塞性肺疾病患者中诱发支气管收缩。在这种情况下，它不仅可用于辅助诊断，还可用于监测患者对类固醇治疗的反应。哮喘患者肺部的腺苷水平升高，表明通过腺苷受体信号通路的通量更大。体外研究表明，腺苷可通过释放促炎细胞因子和趋化因子进入导致慢性炎症发生的途径。动物研究表明，仅仅提高小鼠体内的腺苷水平就足以诱发具有哮喘和慢性阻塞性肺疾病特征的肺部表型。
确定调节哮喘和慢性阻塞性肺疾病慢性本质的介质对于治疗选择的进展至关重要。腺苷已被证明与促进慢性肺病中所见的炎症和气道重塑有关，因此成为一个有吸引力的治疗靶点。
