Participation of cAMP and cAMP-dependent protein kinase in beta-adrenoceptor-mediated interleukin-1 beta mRNA induction in cultured microglia.

We previously reported evidence of beta-adrenoceptor-mediated induction of IL-1 beta mRNA in the rat hypothalamus. The present in vitro studies using northern blot analysis showed that the beta-adrenoceptor agonist isoproterenol (1 x 10(-8) to 1 x 10(-5) M) caused a marked induction of IL-1 beta mRNA in microglia, but not in astrocytes. This induction was remarkably suppressed by pretreatment of cells with the beta-adrenoceptor antagonist propranolol. These phenomena were confirmed by in situ hybridization with digoxigenin-labelled IL-1 beta RNA probe. Furthermore, dibutyryl cyclicAMP (dbcAMP) (5 x 10(-4) and 5 x 10(-5) M) markedly induced IL-1 beta mRNA in microglia. The intracellular level of cAMP in microglia was elevated in a dose-dependent manner when they were treated with isoproterenol, and this elevation was completely blocked by propranolol. The induction of IL-1 beta mRNA by either isoproterenol or dbcAMP was strongly inhibited by a cAMP-dependent protein kinase inhibitor, H8. These results, taken together, suggest that (1) microglia primarily induce IL-1 beta mRNA by stimulation of beta-adrenoceptors, and (2) cAMP and cAMP-dependent protein kinase presumably participate in a signal transduction mechanism involved in the induction of IL-1 beta mRNA via beta-adrenoceptors.