A3 adenosine receptor signaling influences pulmonary inflammation and fibrosis

Eva Morschl, Jose G. Molina, Jonathan B. Volmer, Amir Mohsenin, Ralph S. Pero, Jeong Soo Hong, Farrah Kheradmand, James J. Lee, Michael R. Blackburn

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Adenosine is a signaling molecule produced during conditions that cause cellular stress or damage. This signaling pathway is implicated in the regulation of pulmonary disorders through the selective engagement of adenosine receptors. The goal of this study was to examine the involvement of the A 3 adenosine receptor (A3R) in a bleomycin model of pulmonary inflammation and fibrosis. Results demonstrated that A 3R-deficient mice exhibit enhanced pulmonary inflammation that included an increase in eosinophils. Accordingly, there was a selective up-regulation of eosinophil-related chemokines and cytokines in the lungs of A3R-deficient mice exposed to bleomycin. This increase in eosinophil numberswas accompanied by a decrease in the amount of extracellular eosinophil peroxidase activity in lavage fluid from A3R-deficient mice exposed to bleomycin, an observation suggesting that the A3R is necessary for eosinophil degranulation in this model. Despite an increase in inflammatory metrics associated with A3R-deficient mice treated with bleomycin, there was little difference in the degree of pulmonary fibrosis. Examination of fibrotic mediators demonstrated enhanced transforming growth factor (TGF)-β1 expression, but not a concomitant increase in TGF-β1 activity. This was associated with the loss of expression of matrix metalloprotease 9, an activator of TGF-β1, in alveolar macrophages and airway mast cells in the lungs of A3R-deficient mice. Together, these results suggest that the A3R serves antiinflammatory functions in the bleomycin model, and is also involved in regulating the production of mediators that can impact fibrosis.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Issue number6
StatePublished - Dec 1 2008


  • Adenosine receptors
  • Eosinophil
  • Extracellular matrix
  • Inflammation
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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