Distinct roles for the A2B adenosine receptor in acute and chronic stages of bleomycin-induced lung injury.

Abstract

Adenosine is an extracellular signaling molecule that is generated in response to cell injury where it orchestrates tissue protection and repair. Whereas adenosine is best known for promoting anti-inflammatory activities during acute injury responses, prolonged elevations can enhance destructive tissue remodeling processes associated with chronic disease states. The generation of adenosine and the subsequent activation of the adenosine 2B receptor (A(2B)R) is an important processes in the regulation of both acute and chronic lung disease. The goal of this study was to examine the contribution of the A(2B)R in models of bleomycin-induced lung injury that exhibit varying degrees of acute and chronic injury. Intratracheal bleomycin exposure results in substantial acute lung injury followed by progressive fibrosis. In this model, genetic removal of the A(2B)R resulted in enhanced loss of barrier function and increased pulmonary inflammation, with few differences in indexes of pulmonary fibrosis. These results support an anti-inflammatory role for this receptor in this model of acute lung injury. In contrast, systemic exposure of mice to bleomycin resulted in modest acute lung injury together with progressive pulmonary fibrosis. In this model, the effects of A(2B)R removal on acute lung injury were negligible; however, there were substantial reductions in pulmonary fibrosis, supporting a profibrotic role for this receptor. A(2B)R-dependent regulation of IL-6 production was identified as a potential mechanism involved in the diminished pulmonary fibrosis seen in A(2B)R knockout mice exposed to i.p. bleomycin. These studies highlight the distinct roles of A(2B)R signaling during acute and chronic stages of lung injury.

• Authors: Yang Zhou, Daniel J Schneider, Eva Morschl, Ling Song, Mesias Pedroza, Harry Karmouty-Quintana, Thuy Le, Chun-Xiao Sun, Michael R Blackburn
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 2 Pg. 1097-106 (Jan 15 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21149612 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Inflammation Mediators
• Receptor, Adenosine A2B
• Bleomycin

Topics

• Acute Disease
• Acute Lung Injury (chemically induced, metabolism, pathology)
• Animals
• Bleomycin (toxicity)
• Chronic Disease
• Inflammation Mediators (metabolism, physiology)
• Intubation, Intratracheal
• Lung (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pulmonary Fibrosis (chemically induced, metabolism, pathology)
• Receptor, Adenosine A2B (deficiency, genetics, physiology)