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This concept has been challenged by the finding that genetic removal of A2B receptors leads to exaggerated responses in models of acute inflammation. Therefore, the goal of our study was to determine the effects of A2B receptor gene ablation in the context of ovalbumin-induced chronic pulmonary inflammation. We found that repetitive airway allergen challenge induced a significant increase in adenosine levels in fluid recovered by bronchoalveolar lavage. Genetic ablation of A2B receptors significantly attenuated allergen-induced chronic pulmonary inflammation, as evidenced by a reduction in the number of bronchoalveolar lavage eosinophils and in peribronchial eosinophilic infiltration. The most striking difference in the pulmonary inflammation induced in A2B receptor knockout (A2BKO) and wild-type mice was the lack of allergen-induced IL-4 release in the airways of A2BKO animals, in line with a significant reduction in IL-4 protein and mRNA levels in lung tissue. In addition, attenuation of allergen-induced transforming growth factor\u2013\u03b2 release in airways of A2BKO mice correlated with reduced airway smooth muscle and goblet cell hyperplasia\/hypertrophy. In conclusion, genetic removal of A2B adenosine receptors in mice leads to inhibition of allergen-induced chronic pulmonary inflammation and airway remodeling. These findings are in agreement with previous pharmacologic studies suggesting a deleterious role for A2B receptor signaling in chronic lung inflammation.<\/jats:p>","DOI":"10.1165\/rcmb.2008-0391oc","type":"journal-article","created":{"date-parts":[[2009,6,25]],"date-time":"2009-06-25T22:05:21Z","timestamp":1245967521000},"page":"564-571","source":"Crossref","is-referenced-by-count":47,"title":["Attenuation of Chronic Pulmonary Inflammation in A2B Adenosine Receptor Knockout Mice"],"prefix":"10.1093","volume":"42","author":[{"given":"Rinat","family":"Zaynagetdinov","sequence":"first","affiliation":[{"name":"Divisions of Cardiovascular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Ryzhov","sequence":"additional","affiliation":[{"name":"Divisions of Cardiovascular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyong","family":"Yin","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey V.","family":"Novitskiy","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasia","family":"Goleniewska","sequence":"additional","affiliation":[{"name":"Allergy\/Pulmonary, and Critical Care Medicine, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliy V.","family":"Polosukhin","sequence":"additional","affiliation":[{"name":"Allergy\/Pulmonary, and Critical Care Medicine, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn C.","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Allergy\/Pulmonary, and Critical Care Medicine, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Allergy\/Pulmonary, and Critical Care Medicine, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Morschl","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"R. 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