Adenosine signaling and the regulation of chronic lung disease.

Chronic lung diseases such as asthma, chronic obstructive pulmonary disease and interstitial lung disease are characterized by inflammation and tissue remodeling processes that compromise pulmonary function. Adenosine is produced in the inflamed and damaged lung where it plays numerous roles in the regulation of inflammation and tissue remodeling. Extracellular adenosine serves as an autocrine and paracrine signaling molecule by engaging cell surface adenosine receptors. Preclinical and cellular studies suggest that adenosine plays an anti-inflammatory role in processes associated with acute lung disease, where activation of the A(2A)R and A(2B)R has promising implications for the treatment of these disorders. In contrast, there is growing evidence that adenosine signaling through the A(1)R, A(2B)R and A(3)R may serve pro-inflammatory and tissue remodeling functions in chronic lung diseases. This review discusses the current progress of research efforts and clinical trials aimed at understanding the complexities of these signaling pathway as they pertain to the development of treatment strategies for chronic lung diseases.