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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/L1335    most recent 00416.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Nadeem, A. Articles by Jamal Mustafa, S. Search for Related Content PubMed PubMed Citation Articles by Nadeem, A. Articles by Jamal Mustafa, S.

Enhanced airway reactivity and inflammation in A_2A adenosine receptor-deficient allergic mice

¹Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, West Virginia; ²Department of Pharmacology, East Carolina University, Greenville, North Carolina; and ³Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Université Libre de Bruxelles, Brussels, Belgium

Submitted 19 October 2006 ; accepted in final form 3 February 2007

A_2A adenosine receptor (A_2AAR) has potent anti-inflammatory properties, which may be important in the regulation of airway reactivity and inflammation. Inflammatory cells that possess A_2AAR also produce nitrosative stress, which is associated with pathophysiology of asthma, so we hypothesized that A_2AAR deficiency may lead to increased airway reactivity and inflammation through nitrosative stress. Thus the present study was carried out to investigate the role of A_2AAR on airway reactivity, inflammation, NF-B signaling, and nitrosative stress in A_2AAR knockout (KO) and wild-type (WT) mice using our murine model of asthma. Animals were sensitized intraperitoneally on days 1 and 6 with 200 µg of ragweed, followed by aerosolized challenges with 0.5% ragweed on days 11, 12, and 13, twice a day. On day 14, airway reactivity to methacholine was assessed as enhanced pause (Penh) using whole body plethysmography followed by bronchoalveolar lavage (BAL) and lung collection for various analyses. Allergen challenge caused a significant decrease in expression of A_2AAR in A_2A WT sensitized mice, with A_2AAR expression being undetected in A_2A KO sensitized group leading to decreased lung cAMP levels in both groups. A_2AAR deletion/downregulation led to an increase in Penh to methacholine and influx of total cells, eosinophils, lymphocytes, and neutrophils in BAL with highest values in A_2A KO sensitized group. A_2A KO sensitized group further had increased NF-B expression and nitrosative stress compared with WT sensitized group. These data suggest that A_2AAR deficiency leads to airway inflammation and airway hyperresponsiveness, possibly via involvement of nitrosative stress in this model of asthma.

NF-B signaling

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