title: Oxidative/nitrosative stress selectively altered A(2B) adenosine receptors in chronic obstructive pulmonary disease.
abstract: The primary aim of this study was to investigate adenosine receptors (ARs) in bronchoalveolar lavage (BAL) macrophages from patients with chronic obstructive pulmonary disease (COPD) and age-matched healthy smokers. A(2B)ARs were significantly decreased in BAL macrophages from patients with COPD when compared with healthy smokers. The effect of proinflammatory cytokines and oxidative/nitrosative stress on AR expression and function in U937 cells before and after PMA treatment was evaluated. IL-1beta and TNF-alpha treatment up-regulated A(2A)- and A(3)ARs but not A(1)- or A(2B)ARs, whereas IL-6 did not modify AR expression. In contrast, oxidative/nitrosative stress selectively decreased A(2B)AR expression, which was associated with a reduction in the potency of the adenosine agonist 5'-N-ethylcarboxamideadenosine (NECA) to induce cAMP. Further, the ability of NECA to enhance cell proliferation was increased after oxidative/nitrosative stress. The specific involvement of A(2B)ARs was investigated by using potent and selective A(2B)AR antagonist and by A(2B)AR knockdown using siRNA and demonstrated responses similar to those obtained with oxidative/nitrosative stress. N-acetylcysteine (NAC), an antioxidant agent, counteracted the decrease in A(2B)AR expression, as well as the altered NECA effects on cAMP and cell proliferation. These findings highlight the central role of A(2B)ARs in alveolar macrophages, suggesting that their modulation could represent an innovative pharmacological strategy to manage COPD.-Varani, K., Caramori, G., Vincenzi, F., Tosi, A., Barczyk, A., Contoli, M., Casolari, P., Triggiani, M., Hansel, T., Leung, E., MacLennan, S., Barnes, P. J., Fan Chung, K., Adcock, I., Papi, A., Borea, P. A. Oxidative/nitrosative stress selectively altered A(2B) adenosine receptors in chronic obstructive pulmonary disease.
authors.affiliation: Department of Clinical and Experimental Medicine, Pharmacology Unit, University of Ferrara, via Fossato di Mortara 17-19, 44100 Ferrara, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caramori
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vincenzi
authors.forename: Alice
authors.initials: A
authors.lastname: Tosi
authors.forename: Adam
authors.initials: A
authors.lastname: Barczyk
authors.forename: Marco
authors.initials: M
authors.lastname: Contoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Casolari
authors.forename: Massimo
authors.initials: M
authors.lastname: Triggiani
authors.forename: Trevor
authors.initials: T
authors.lastname: Hansel
authors.forename: Edward
authors.initials: E
authors.lastname: Leung
authors.forename: Stephen
authors.initials: S
authors.lastname: Maclennan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000368:Aged; D018893:Bronchoalveolar Lavage; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D034741:RNA, Small Interfering / Q000494:pharmacology; D043704:Receptor, Adenosine A2B / Q000096:biosynthesis* / Q000235:genetics; D012907:Smoking / Q000378:metabolism / Q000473:pathology; D020298:U937 Cells; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D016207:Cytokines; D016166:Free Radical Scavengers; D034741:RNA, Small Interfering; D043704:Receptor, Adenosine A2B; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000111:Acetylcysteine