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Keywords:

  • multiple sclerosis;
  • cathepsin B;
  • adrenergic regulation;
  • macrophages

Abstract

In order to investigate the possible modulation of macrophage function by the autonomic nervous system, the effect of adrenergic agonists and antagonists on interferon (IFN)-γ-induced increases in cathepsin B (CB) in a macrophage-like cell line was studied. It has been shown previously that IFN-γ induces increased CB activity in phorbol myristate acetate (PMA)-primed THP-1 cells. Isoproterenol (ISO) (10μm), a mixed β-receptor agonist, increased the induction of CB activity in the cells but norepinephrine (10μm) and epinephrine (10μm), the α and β receptor agonists, had little effect. The addition of the mixed α-receptor antagonist phentolamine (10μm) had no effect on ISO induced increases but the mixed β-receptor antagonist propranolol (10μm) and the selective β1-receptor antagonist atenolol produced significant inhibition. These results suggest that the activation of β-receptors could be involved in the induction of CB activity in macrophages and provide a possible mechanism for the regulation of macrophage effector function by the autonomic nervous system. Dibutyryl cAMP (1mm) alone also induced increases in CB in THP-1 cells, and H-89 or HA1004 abrogated the effect of dibutyryl cAMP, suggesting that the effect of ISO on CB could be through the elevation of cAMP and the activation of cAMP-dependent protein kinases.