Adenosine A 2A receptors promote adenosine-stimulated wound healing in bronchial epithelial cells

• Published in: American journal of physiology. Lung cellular and molecular physiology 2006-05, Vol.290 (5), p.L849-L855
• Main Authors: Allen-Gipson, D. S., Wong, J., Spurzem, J. R., Sisson, J. H., Wyatt, T. A.
• Format: Article
• Language: English
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00373.2005

Adenosine produces a wide variety of physiological effects through the activation of specific adenosine receptors (A 1 , A 2A , A 2B , A 3 ). Adenosine, acting particularly at the A 2A adenosine receptor (A 2A AR), 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 A 2A AR as the main adenosine receptor responsible for altering the kinetics of wound closure. We hypothesized that A 2A AR 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 A 1 , A 2A , A 2B and A 3 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 A 2A AR. 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 A 2A AR agonist 5′-( N-cyclopropyl)carboxamidoadenosine (CPCA) augmented wound closure, with a maximal closure rate occurring between 4 and 6 h. Inhibition of A 2A AR with ZM-241385, a known A 2A AR 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 A 2A AR. Collectively, the data suggest that the A 2A AR is involved in BEC adenosine-stimulated wound healing and may prove useful in understanding purinergic-mediated actions on airway epithelial repair.