title: Differential expression of adenosine receptors in human neutrophils: up-regulation by specific Th1 cytokines and lipopolysaccharide.
abstract: Four types of adenosine receptors have been identified in different tissues and cell types, namely, A1, A2A, A2B, and A3 receptors. We report that A2AR but not A2BR mRNA in freshly isolated polymorphonuclear neutrophils (PMN) is maximally up-regulated after 4 h stimulation with lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-alpha) and to a lesser extent, with interleukin (IL)-1beta. These effects were maintained up to 21 h. Consistent with changes in A2AR mRNA expression, up-regulation of A2AR protein was also detected after 4 h of LPS or TNF-alpha exposure. Up-regulation of A2AR protein expression was transient and returned to near basal levels after 12 h or 16 h stimulation with TNF-alpha or LPS, respectively. Conversely, IL-1beta failed to promote A2AR protein expression. Suppression of thapsigargin-induced leukotriene synthesis by the selective A2AR agonist CGS-21680 was found to be more pronounced when PMN were cultured for 4 h with LPS or TNF-alpha. In contrast, the up-regulation of A2AR has no impact on CGS-21680-induced inhibition of phospholipase D activation and superoxide production in response to formyl-Met-Leu-Phe. These results demonstrate that the A2AR is up-regulated by specific T helper cell type 1 cytokines and LPS. Although this could represent a potential feedback mechanism to control inflammation, the effect of A2AR up-regulation varied depending on the stimulus used to stimulate PMN functional responses after their incubation with proinflammatory mediators.
authors.affiliation: Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon C.H.U.L., 2705 Blvd. Laurier, Sainte-Foy, Québec, Canada G1V 4G2.
authors.forename: Andrée
authors.initials: A
authors.lastname: Fortin
authors.forename: Danielle
authors.initials: D
authors.lastname: Harbour
authors.forename: Maria
authors.initials: M
authors.lastname: Fernandes
authors.forename: Pierre
authors.initials: P
authors.lastname: Borgeat
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bourgoin
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D015289:Leukotrienes / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D010739:Phospholipase D / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000959:Antihypertensive Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D015289:Leukotrienes; D008070:Lipopolysaccharides; D010627:Phenethylamines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester; D010739:Phospholipase D; D000241:Adenosine