beta-adrenoceptor-mediated inhibition of IFN-gamma, IL-3, and GM-CSF mRNA accumulation in activated human T lymphocytes is solely mediated by the beta(2)-adrenoceptor subtype

P Borger, Y Hoekstra, MT Esselink, DS Postma, J Zaagsma, E Vellenga, HF Kauffman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

89 Citations (Scopus)

Abstract

Cytokine gene expression in T lymphocytes is a strictly regulated process, involving both stimulatory and inhibitory signals. beta-Adrenoceptor (beta AR) agonists are widely used in the treatment of asthma and are able to induce an inhibitory signal on immunological responses after binding to their specific receptors. In this study, the characterization of beta AR subtype(s) (beta(1), beta(2), and beta(3)) involved in the regulation of interleukin (IL)-3, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon-gamma (IFN-gamma) mRNA accumulation was studied by using various beta AR agonists and antagonists. Concanavalin A (Con A)-induced IFN-gamma, GM-CSF, and IL-3 mRNAs are dose-dependently inhibited by the nonselective beta AR agonist isoproterenol and by the selective beta(2)AR agonist fenoterol. IL-4 mRNA accumulation was not susceptible to beta AR stimulation. The observed inhibition on IFN-gamma, GM-CSF, and IL-3 mRNA was blocked by the selective beta(2)AR antagonist ICI 118,551 (10(-6) M) and by timolol (10(-6) M), a nonselective antagonist. The selective beta(1)AR antagonist atenolol (0.3 x 10(-6) M) did not have any effect. Secretion of GMCSF protein in the presence of increasing concentrations of isoproterenol followed a similar pattern as observed for GM-CSF mRNA. In addition, the beta AR-mediated inhibition of IFN-gamma, GM-CSF, and IL-3 mRNA accumulation and GM-CSF protein secretion were related to the accumulation of intracellular cyclic adenosine monophosphate (cAMP) levels. Although beta(3)AR mRNA was detectable in Con A-activated T lymphocytes, we could not demonstrate a functional activity in the regulation of cytokine expression: the beta(3)AR agonist BRL 37344 had no effect on the accumulation of the studied cytokine mRNAs, and did not significantly affect cellular cAMP levels. These data demonstrate that beta-agonist-induced inhibition of IFN-gamma, GM-CSF, and IL-3 mRNA accumulation is solely mediated by beta(2)-adrenoceptors.

Original languageEnglish
Pages (from-to)400-407
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume19
Issue number3
Publication statusPublished - Sep-1998

Keywords

  • ADRENERGIC RECEPTORS
  • CYCLIC-AMP
  • CELLS
  • INTERLEUKIN-2
  • EXPRESSION
  • MECHANISMS
  • CAMP
  • ANTAGONISTS
  • SYSTEM

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