title: Lipopolysaccharide and TNF-alpha modify adenosine A(2A) receptor expression and function in equine monocytes.
abstract: Stimulation of adenosine A(2A) receptors results in anti-inflammatory effects in a variety of cell types. Lipopolysaccharide (LPS) and pro-inflammatory cytokines, such as TNF-alpha and IL-1, have been reported to up-regulate the expression of adenosine A(2A) receptors and thereby enhance the functional activity of adenosine A(2A) receptors in human and murine monocyte/macrophage cell lines and in monocytes/macrophages isolated from those species. In this study, we investigated the effects of LPS and TNF-alpha on the expression and functional activity of adenosine A(2A) receptors in isolated equine peripheral blood monocytes. The results of this study indicate that LPS and TNF-alpha up-regulate the transcription of adenosine A(2A) receptors for up to 24h; the response to LPS was of greater magnitude than the response to TNF-alpha. In this study, incubation with LPS, but not with TNF-alpha, resulted in down-regulation of adenosine A(3) receptor mRNA expression. Furthermore, incubation of these cells with LPS significantly increases the surface density of adenosine A(2A) receptors, and incubation with low concentrations of either LPS or TNF-alpha significantly increases the potency of the adenosine A(2A) receptor agonist, ATL313, to inhibit LPS-induced production of TNF-alpha. These findings suggest that the increased expression of adenosine A(2A) receptors and the enhanced functional potency of adenosine A(2A) receptor agonists after exposure to pro-inflammatory substances such as LPS or TNF-alpha may render adenosine A(2A) receptor agonists particularly important in the treatment of the systemic inflammatory response syndrome that occurs secondary to endotoxemia and bacterial infections in adult horses and neonatal foals.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States.
authors.forename: Wan-chun
authors.initials: WC
authors.lastname: Sun
authors.forename: Londa J
authors.initials: LJ
authors.lastname: Berghaus
authors.forename: James N
authors.initials: JN
authors.lastname: Moore
authors.forename: David J
authors.initials: DJ
authors.lastname: Hurley
authors.forename: Michel L
authors.initials: ML
authors.lastname: Vandenplas
authors.forename: Robert
authors.initials: R
authors.lastname: Thompson
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D006734:Horse Diseases / Q000188:drug therapy / Q000378:metabolism; D006736:Horses / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary; D014227:Triazines / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C510376:ATL 313; D058908:Adenosine A2 Receptor Agonists; D017931:DNA Primers; D008070:Lipopolysaccharides; D010880:Piperidines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D011994:Recombinant Proteins; D014227:Triazines; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C097270:ZM 241385