Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells.
Brain macrophages (ameboid microglial cells) purified to homogeneity and cultured in vitro synthesize and release IL-1 and TNF upon stimulation with lipopolysaccharide (LPS). This induction can be measured at the levels of transcription and translation. In the present study we have analysed whether certain compounds normally present in the nervous tissue could regulate cytokine production by brain macrophages. We demonstrate that the beta-adrenergic agonist isoproterenol, at a concentration of 10(-7) M; inhibits the LPS-induced transcription and release of TNF alpha. At the same concentration, isoproterenol increases the accumulation of IL-1 alpha and IL-1 beta mRNAs. In spite of its strong effect on IL-1 mRNA accumulation, the adrenergic agonist did not enhance IL-1 activity produced by microglial cells. On the contrary, as is the case for TNF, the LPS-induced production of IL-1 was inhibited by isoproterenol. The effects of isoproterenol on cytokine production specifically involve the beta 2 and not the beta 1 adrenergic receptor. It thus appears (i) that the accumulation of mRNAs coding for TNF alpha on one hand and IL-1 alpha and beta on the other is regulated in two opposite ways by the stimulation of the beta 2-adrenergic receptor and (ii) that mRNA accumulation and cytokine production and secretion are not necessarily coupled.
Hetier
E
E
CNRS URA 1414, Ecole Normale Supérieure, Paris, France.
Ayala
J
J
Bousseau
A
A
Prochiantz
A
A
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000318:Adrenergic beta-Agonists; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D007545:Isoproterenol