Dual β-adrenergic modulation in the immune system: Stimulus-dependent effect of isoproterenol on MAPK activation and inflammatory mediator production in macrophages

Judith Szelenyi, Zsolt Selmeczy, Anna Brozik, David Medgyesi, Maria Magocsi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

This is the first study to demonstrate that the interaction between β-adrenoceptor activation, and the production of inflammatory mediators can be modulated in opposite ways by two inflammatory stimuli, namely, protein kinase C (PKC)-activating phorbol myristyl acetate (PMA) and lipopolysaccharide (LPS). We provided evidence that isoproterenol treatment, when combined with phorbol ester increased the production of tumor necrosis factor-alpha, interleukin-12, and nitric oxide in murine macrophages, as well as in human monocytes and differentiated PLB-985 cells, while in agreement with earlier findings, it decreased inflammatory mediator production in combination with LPS stimulation. The contrasting effect on inflammatory mediator production, shown for the PMA and LPS activated cells was accompanied by parallel changes in activation of ERK1/2 and p38 MAPKs. Thus, isoproterenol significantly increased MAPK activation (phosphorylation) in PMA-treated cells and, conversely, it decreased the activation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 in LPS-stimulated cells. The opposing effects of isoproterenol on LPS-induced versus PMA-induced mediator production and the concurrent changes in MAPK activation highlight the role of this kinase pathway in macrophage activation and provide new insights regarding the flexible ways through which β-adrenoceptor stimulation can modulate the inflammatory response in macrophages. Our results challenge the dogma that β-adrenoceptor signaling is only immunosuppressive, and offer potential opportunities for new therapeutic approaches in the treatment of inflammatory and autoimmune diseases.

Original languageEnglish
Pages (from-to)94-103
Number of pages10
JournalNeurochemistry international
Volume49
Issue number1
DOIs
Publication statusPublished - Jul 1 2006

    Fingerprint

Keywords

  • Dichotomous effects of isoproterenol
  • Inflammation
  • MAPK
  • Macrophage
  • Stimulus-dependent immunomodulation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this