Editors' ChoiceChronic lung disorders

Emerging Targets

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Science Translational Medicine  03 Mar 2010:
Vol. 2, Issue 21, pp. 21ec32
DOI: 10.1126/scitranslmed.3000997

Chronic obstructive pulmonary disease (COPD)—an inflammatory condition characterized by bronchitis and emphysema—and idiopathic pulmonary fibrosis (IPF)—a disease in which excess connective tissue is deposited in the lung—are among the world’s deadliest lung diseases. The pathways that drive their progression are relatively uncharacterized; overactive wound-healing may play a role. The nucleoside adenosine can act as an extracellular signaling molecule that regulates tissue injury and repair, and studies in mouse models suggest that activation of adenosine receptor–related signaling causes proinflammatory and profibrotic effects related to the progression of these diseases. Now, Zhou et al. provide evidence that components of adenosine metabolism and signaling are altered in the lungs of patients with COPD or IPF. The authors found increased transcript levels of CD73 (the main enzyme responsible for extracellular adenosine production) and the adenosine receptor A2BR in surgical lung biopsy tissues of advanced COPD and IPF patients as compared with levels in tissues from patients with early or mild disease. Expression of CD73 and A2BR was increased in both COPD and IPF tissues in a class of macrophages that are major contributors to disease maintenance and progression. Additionally, CD73 enzyme activity was increased in diseased tissue, whereas adenosine deaminase activity was reduced, both of which are effects that could contribute to adenosine accumulation. Levels of interleukin-6 (IL-6), IL-8, and osteopontin—proinflammatory and profibrotic mediators that act downstream of A2BR—were also elevated in COPD and IPF samples. Furthermore, blocking A2BR signaling in macrophages from the lungs of patients with severe or late-stage disease reduced proinflammatory cytokine (IL-6 and IL-8) production. These studies suggest that adenosine receptor–based therapeutics could emerge as a potential treatment strategy for chronic airway diseases. Indeed, pharmacological approaches to modulate extracellular adenosine signaling are being evaluated now for their potential uses in other diseases.

Y. Zhou et al., Alterations in adenosine metabolism and signaling in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. PLoS One 5, e9224 (2010). [Full Text]

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