Adenosine A2A receptors promote adenosine-stimulated wound healing in bronchial epithelial cells

D. S. Allen-Gipson, J. Wong, J. R. Spurzem, Joseph Harold Sisson, Todd A Wyatt

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Adenosine produces a wide variety of physiological effects through the activation of specific adenosine receptors (A1, A2A, A2B, A3). Adenosine, acting particularly at the A 2A adenosine receptor (A2AAR), is a potent endogenous anti-inflammatory agent and sensor of inflammatory tissue damage. The complete healing of wounds is the final step in a highly regulated response to injury. Recent studies on epidermal wounds have identified the A2AAR as the main adenosine receptor responsible for altering the kinetics of wound closure. We hypothesized that A2AAR promotes wound healing in bronchial epithelial cells (BECs). To test this hypothesis, the human BEC line BEAS-2B and bovine BECs (BBECs) were used. Real-time RT-PCR of RNA from unstimulated BEAS-2B cells revealed transcriptional expression of A1, A 2A, A2B and A3 receptors. Western blot analysis of lysates from BEAS-2B cells and BBECs detected a single band at 44.7 kDa in both the BECs, indicating the presence of A2AAR. In a wound healing model, we found that adenosine stimulated wound repair in cultured BBECs in a concentration-dependent manner, with an optimal closure rate observed between 4 and 6 h. Similarly, the A2AAR agonist 5′-(N-cyclopropyl) carboxamidoadenosine (CPCA) augmented wound closure, with a maximal closure rate occurring between 4 and 6 h. Inhibition of A2AAR with ZM-241385, a known A2AAR antagonist, impeded wound healing. In addition, ZM-241385 also attenuated adenosine-mediated wound repair. Kinase studies revealed that adenosine-stimulated airway repair activates PKA by ligating A2AAR. Collectively, the data suggest that the A2AAR is involved in BEC adenosine-stimulated wound healing and may prove useful in understanding purinergic-mediated actions on airway epithelial repair.

Original languageEnglish (US)
Pages (from-to)L849-L855
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume290
Issue number5
DOIs
StatePublished - May 1 2006

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Keywords

  • Airway injury
  • Airway repair

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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