Modulation of interferon gamma induced increases in cathepsin B in THP-1 cells by adrenergic agonists and antagonists

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)-gamma-induced increases in cathepsin B (CB) in a macrophage-like cell line was studied. It has been shown previously that IFN-gamma induces increased CB activity in phorbol myristate acetate (PMA)-primed THP-1 cells. Isoproterenol (ISO) (10 micrometers), a mixed beta-receptor agonist, increased the induction of CB activity in the cells but norepinephrine (10 micrometers) and epinephrine (10 micrometers), the alpha and beta receptor agonists, had little effect. The addition of the mixed alpha-receptor antagonist phentolamine (10 micrometers) had no effect on ISO induced increases but the mixed beta-receptor antagonist propranolol (10 micrometers) and the selective beta1-receptor antagonist atenolol produced significant inhibition. These results suggest that the activation of beta-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 (1 mm) 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.