Blackburn Michael R, Vance Constance O, Morschl Eva, Wilson Constance N
Department of Biochemistry and Molecular Biology, The University of Texas-Houston Medical School, Houston, TX 77030, USA.
Handb Exp Pharmacol. 2009(193):215-69. doi: 10.1007/978-3-540-89615-9_8.
Extracellular adenosine is produced in a coordinated manner from cells following cellular challenge or tissue injury. Once produced, it serves as an autocrine- and paracrine-signaling molecule through its interactions with seven-membrane-spanning G-protein-coupled adenosine receptors. These signaling pathways have widespread physiological and pathophysiological functions. Immune cells express adenosine receptors and respond to adenosine or adenosine agonists in diverse manners. Extensive in vitro and in vivo studies have identified potent anti-inflammatory functions for all of the adenosine receptors on many different inflammatory cells and in various inflammatory disease processes. In addition, specific proinflammatory functions have also been ascribed to adenosine receptor activation. The potent effects of adenosine signaling on the regulation of inflammation suggest that targeting specific adenosine receptor activation or inactivation using selective agonists and antagonists could have important therapeutic implications in numerous diseases. This review is designed to summarize the current status of adenosine receptor signaling in various inflammatory cells and in models of inflammation, with an emphasis on the advancement of adenosine-based therapeutics to treat inflammatory disorders.
细胞受到刺激或组织损伤后，细胞外腺苷会以协调的方式产生。一旦产生，它通过与七跨膜G蛋白偶联腺苷受体相互作用，作为自分泌和旁分泌信号分子。这些信号通路具有广泛的生理和病理生理功能。免疫细胞表达腺苷受体，并以多种方式对腺苷或腺苷激动剂作出反应。大量的体外和体内研究已经确定，在许多不同的炎症细胞和各种炎症疾病过程中，所有腺苷受体都具有强大的抗炎功能。此外，腺苷受体激活也被认为具有特定的促炎功能。腺苷信号对炎症调节的强大作用表明，使用选择性激动剂和拮抗剂靶向特定腺苷受体的激活或失活，可能在众多疾病中具有重要的治疗意义。本综述旨在总结腺苷受体信号在各种炎症细胞和炎症模型中的现状，重点是基于腺苷的治疗方法在治疗炎症性疾病方面的进展。
