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Modulation of interleukin-1 and tumor necrosis factor expression by β-adrenergic agonists in mouse ameboid microglial cells

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Summary

Brain macrophages (ameboid microglial cells) purified to homogeneity and cultured in vitro synthesize and release IL-1 and TNF upon stimulation with lipo-polysaccharide (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 β-adrenergic agonist isoproterenol, at a concentration of 10-7 M; inhibits the LPS-induced transcription and release of TNFα. At the same concentration, isoproterenol increases the accumulation of IL-1α and IL-1β 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 β 2 and not the β 1 adrenergic receptor. It thus appears (i) that the accumulation of mRNAs coding for TNFα on one hand and IL-1α and β on the other is regulated in two opposite ways by the stimulation of the β 2-adrenergic receptor and (ii) that mRNA accumulation and cytokine production and secretion are not necessarily coupled.

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Authors and Affiliations

  1. CNRS URA 1414, Ecole Normale Supérieure, 46, Rue d'Ulm, F-75230, Paris Cedex 05, France

    E. Hetier, J. Ayala1 & A. Prochiantz1

  2. Centre de Recherche de Vitry, Rhône poulenc Santé, 13 Quai de Vitry, F-94403, Vitry sur Seine, France

    A. Bousseau

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  1. E. Hetier
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  2. J. Ayala1
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  3. A. Bousseau
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  4. A. Prochiantz1
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Hetier, E., Ayala1, J., Bousseau, A. et al. Modulation of interleukin-1 and tumor necrosis factor expression by β-adrenergic agonists in mouse ameboid microglial cells. Exp Brain Res 86, 407–413 (1991). https://doi.org/10.1007/BF00228965

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  • DOI: https://doi.org/10.1007/BF00228965

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