Adenosine signaling in asthma and chronic obstructive pulmonary disease.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Mohsenin
Amir
A
Department of Biochemistry and Molecular Biology, University of Texas - Houston Medical School, Houston, Texas 77030, USA.
Blackburn
Michael R
MR
D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D000241:Adenosine