title: Differential regulation of cardiac expression of IL-6 and TNF-alpha by A2- and A3-adenosine receptors.
abstract: The proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 have been implicated in the development of congestive heart failure. Adenosine inhibits the expression of TNF-alpha and IL-6 in macrophages. We determined the effect of adenosine on cytokine expression in rat cardiomyocytes and trabecular muscles obtained from patients with cardiomyopathy. In myocytes, adenosine suppressed TNF-alpha mRNA by 40% (P < 0.05) and induced a 4.7-fold increase in IL-6 mRNA (P < 0.05) with a twofold increase in IL-6 protein release (P < 0.001). The effect on TNF-alpha could be replicated by A2 agonist. The effect on IL-6 could be replicated by A3 agonist, but not by A1 and A2 agonists, and was completely suppressed by A3 antagonist. In human trabecular muscles, A2 agonist suppressed TNF-alpha mRNA by 60% (P < 0.05), but adenosine had no effect on IL-6. In the failing heart, IL-6 was immunolocalized to inflammatory cells. Thus A2 and A3 receptors differentially regulate cardiac expression of TNF-alpha and IL-6. Rat cardiomyocytes and the failing human heart respond differently to adenosine.
authors.affiliation: Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Wagner
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: V J
authors.initials: VJ
authors.lastname: Sanders
authors.forename: C F
authors.initials: CF
authors.lastname: McTiernan
authors.forename: A M
authors.initials: AM
authors.lastname: Feldman
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D010210:Papillary Muscles / Q000378:metabolism; D020033:Protein Isoforms / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D020033:Protein Isoforms; D018047:Receptors, Purinergic P1; D014409:Tumor Necrosis Factor-alpha