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.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015152:Blotting, Northern; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D007375:Interleukin-1; D015347:RNA Probes; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol