Activation of adenosine A3 receptors on macrophages inhibits tumor necrosis factor-

Charlene D. McWhinney, Mark W. Dudley, Terry L. Bowlin, Norton P. Peet, Larry Schook, Marita Bradshaw, Mamata De, David R. Borcherding, Carl K. Edwards

Research output: Contribution to journalArticle

Abstract

Murine macrophage-derived tumor necrosis factor alpha (TNF-α) gene expression has been shown to be dramatically induced by bacterial lipopolysaccharide, and to be dependent upon nuclear factor-κB (NF-κB) binding sites in its promoter for the lipopolysaccharide induction. Murine J774.1 macrophage cells were found to predominately express the adenosine A3 receptor RNA relative to adenosine A1 receptor or adenosine A2 receptor RNA. Adenosine receptor agonists, in a dose-dependent manner characteristic of the adenosine A3 receptor, blocked the endotoxin induction of the TNF-α gene and TNF-α protein expression in the J774.1 macrophage cell line. The adenosine A3 receptor antagonist BW-1433 dose-dependently reversed this adenosine inhibitory effect on TNF-α gene expression. Thus, the binding of adenosine receptor agonists to the adenosine A3 receptor interrupts the endotoxin CD14 receptor signal transduction pathway and blocks induction of cytokine TNF-α, revealing a novel cross-talk between the murine adenosine A3 receptor and the endotoxin CD14 receptor in J774.1 macrophages.

Original languageEnglish (US)
Pages (from-to)209-216
Number of pages8
JournalEuropean Journal of Pharmacology
Volume310
Issue number2-3
DOIs
StatePublished - Aug 29 1996

Keywords

  • Adenosine A receptor
  • Cross-talk
  • Macrophage
  • Receptor
  • TNF-α (tumor necrosis factor α) inhibition

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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    McWhinney, C. D., Dudley, M. W., Bowlin, T. L., Peet, N. P., Schook, L., Bradshaw, M., De, M., Borcherding, D. R., & Edwards, C. K. (1996). Activation of adenosine A3 receptors on macrophages inhibits tumor necrosis factor-. European Journal of Pharmacology, 310(2-3), 209-216. https://doi.org/10.1016/0014-2999(96)00272-5