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Adenosine signaling and the regulation of chronic lung disease

Department of Biochemistry and Molecular Biology, The University of Texas-Houston Medical School, 6431 Fannin St., Houston, Texas, 77030, United States
Pharmacology [?] Therapeutics (Impact Factor: 7.75). 07/2009; 123(1):105-116. DOI: 10.1016/j.pharmthera.2009.04.003

ABSTRACT 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 A2AR and A2BR has promising implications for the treatment of these disorders. In contrast, there is growing evidence that adenosine signaling through the A1R, A2BR and A3R 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.

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    • "Chronic lung diseases are characterized by inflammation with dysregulated wound healing and tissue remodeling, although little is known about the underlying molecular mechanisms. Evidence from both clinical and animal studies demonstrates that adenosine signaling is involved in the regulation of chronic lung diseases (5-9). Adenosine levels are elevated in exhaled condensates and bronchoalveolar lavage fluid of patients with chronic lung diseases such as asthma and chronic obstructive pulmonary disease COPD (10, 11), whereas diminishing levels of adenosine in animal models of chronic lung disease results in resolution of airway inflammation and remodeling (5). "
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    Pediatric Research 12/2013; 75(3). DOI:10.1038/pr.2013.233 · 2.84 Impact Factor
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    • "Accumulating evidence has suggested that elevated adenosine levels in lung are associated with chronic lung diseases in both human and animal models [12] [17]. An indepth understanding of the biological relevance of Ada in lung will benefit our general understanding of COPD. "
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    • "One inflammatory mediator common to both airway diseases is adenosine, making its receptor signaling pathway a therapeutic target for asthma and COPD. Adenosine levels were increased in the plasma, lavage fluid, and exhaled breath condensate of patients with asthma and COPD, and in animal models that exhibited features of chronic airway disease.72 Moreover, the inhalation of adenosine induced bronchoconstriction in patients with asthma and COPD.73 "
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