1. Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.
- Author
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Densmore JC, Schaid TR, Jeziorczak PM, Medhora M, Audi S, Nayak S, Auchampach J, Dwinell MR, Geurts AM, and Jacobs ER
- Subjects
- Adenosine pharmacology, Animals, Ischemia, RNA, Messenger analysis, Rats, Receptor, Adenosine A2A analysis, Receptor, Adenosine A2A genetics, Receptor, Adenosine A2B analysis, Receptor, Adenosine A2B genetics, Cryptogenic Organizing Pneumonia prevention & control, Lung Injury metabolism, Receptor, Adenosine A2B physiology, Signal Transduction physiology
- Abstract
Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia., Materials and Methods: Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A
2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2A AR) and A2B adenosine receptor (A2B AR) mRNA and protein were quantified., Results: Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2B AR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2A AR mRNA and protein concentrations remained unchanged following ischemia. A2B AR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes., Conclusion: Increased A2B AR and adenosine following unilateral lung ischemia as well as more BOOP in A2B AR mutant rats implicate a protective role for A2B AR signaling in countering ischemic lung injury.- Published
- 2017
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