PMID: 11311890Apr 20, 2001Paper

beta-adrenergic receptor stimulation selectively inhibits IL-12p40 release in microglia

Brain Research
Marco PrinzUwe-Karsten Hanisch

Abstract

The cytokine interleukin-12 (IL-12) is mainly produced in response to bacterial or parasitic infections. We examined the capacity of mouse brain microglia to release IL-12 forms upon challenge with bacterial lipopolysaccharide (LPS) and studied its modulation by sympathomimetics. LPS evoked the release of IL-12p40 whereas the heterodimeric form, IL-12p70 was virtually undetectable. Sympathomimetics such as salbutamol dose-dependently inhibited IL-12p40 release, whereas the production of IL-6, TNFalpha and MIP-1alpha was only marginally influenced. The inhibitory effect of salbutamol could be abolished by beta-antagonists, such as oxprenolol. The cAMP-elevating agent forskolin could mimic the effects of beta-agonists, indicating that IL-12p40 release inhibition involves intracellular cAMP accumulation. While microglial IL-12p40 may play a role in the regulation of IL-12p70 bioactivity, microglial release is itself modulated by IL-12p70. Recombinant IL-12p70 was found to enhance the LPS-evoked release of MIP-1alpha and to have a biphasic effect on both TNFalpha and MIP-1alpha with release augmentation at lower and attenuation at higher doses. Finally, no functional correlation was found between the release of IL-12p40 and the ind...Continue Reading

Citations

Jun 19, 2015·Physiological Reviews·Vidar GundersenLinda Hildegard Bergersen
Jun 24, 2016·Stroke and Vascular Neurology·Huan LiuXiaoming Hu
Aug 21, 2002·Biological & Pharmaceutical Bulletin·Yoichi Nakamura
Sep 25, 2002·Journal of Neuroscience Research·Kenji F TanakaMakoto Sawada
Oct 16, 2002·Glia·Uwe-Karsten Hanisch
Sep 29, 2006·Glia·Katrin Färber, Helmut Kettenmann
Apr 30, 2011·Physiological Reviews·Helmut KettenmannAlexei Verkhratsky
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Apr 4, 2013·The Journal of Biological Chemistry·Stefka Gyoneva, Stephen F Traynelis
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