PARTICIPATION OF CAMP AND CAMP-DEPENDENT PROTEIN-KINASE IN BETA-ADRENOCEPTOR-MEDIATED INTERLEUKIN-1-BETA MESSENGER-RNA INDUCTION IN CULTURED MICROGLIA

We previously reported evidence of beta-adrenoceptor-mediated inductio n of IL-1 beta mRNA in the rat hypothalamus. The present in vitro stud ies using northern blot analysis showed that the P-adrenoceptor agonis t 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-adre noceptor antagonist propranolol. These phenomena were confirmed by in situ hybridization with digoxigenin-labelled IL-1(b)eta RNA probe. Fur thermore, dibutyryl cyclicAMP (dbcAMP) (5 x 10(-4) and 5 x 10(-5) M) m arkedly induced IL-1 beta mRNA in microglia. The intracellular level o f cAMP in microglia was elevated in a dose-dependent manner when they were treated with isoproterenol, and this elevation was completely blo cked by propranolol. The induction of IL-1 beta mRNA by either isoprot erenol or dbcAMP was strongly inhibited by a cAMP-dependent protein ki nase inhibitor, H8. These results, taken together, suggest that (1) mi croglia primarily induce IL-1 beta mRNA by stimulation of beta-adrenoc eptors, and (2) cAMP and cAMP-dependent protein kinase presumably part icipate in a signal transduction mechanism involved in the induction o f IL-1 beta mRNA via beta-adrenoceptors.