title: Modification of cytokine milieu by A2A adenosine receptor signaling--possible application for inflammatory diseases.
abstract: Pro-inflammatory cytokine TNF-alpha (TNF) production from in vitro lipopolysaccharide (LPS)-stimulated human peripheral blood CD14+ cells (PB-CD14) was inhibited by A2A adenosine receptor (AdoR) (A2AR) or beta2 adrenergic receptor (ADR) (beta2R) signaling in a concentration-dependent manner. These inhibitory effects were presumably mediated by the increase in intracellular cAMP. Furthermore A2AR agonist and beta2R agonist synergistically inhibited the TNF production of LPS-stimulated PB-CD14 cells. These results suggest that the anti-inflammatory effect of extracellular adenosine is, at least in part, due to the modification of the cytokine milieu via A2A signaling, and that the targeting of both A2AR and beta2R may have strong therapeutic potential for the inflammatory diseases.
authors.affiliation: Department Biomedical Informatics, Kobe University Graduate School of Medicine, Japan. mKoshiba@med.kobe-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Koshiba
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamachi
authors.forename: H
authors.initials: H
authors.lastname: Kosaka
authors.forename: T
authors.initials: T
authors.lastname: Nakazawa
authors.forename: G
authors.initials: G
authors.lastname: Tsuji
authors.forename: S
authors.initials: S
authors.lastname: Kumagai
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D043705:Receptor, Adenosine A2A; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP