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

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Item Type:	Article
Title:	beta-adrenergic receptor stimulation selectively inhibits IL-12p40 release in microglia
Creators Name:	Prinz, M., Haeusler, K.G., Kettenmann, H. and Hanisch, U.K.
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, TNF{alpha} and MIP-1α 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-1α and to have a biphasic effect on both TNFα and MIP-1{alpha} with release augmentation at lower and attenuation at higher doses. Finally, no functional correlation was found between the release of IL-12p40 and the induction of Kv1.3 potassium channels, another marker of microglial activation. Taken together, {beta}2-adrenoreceptor-mediated effects on microglial cyto- and chemokine release via cAMP accumulation could modulate inflammatory cascades during bacterial infections.
Keywords:	{Beta}2-Adrenoreceptor, Chemokines, Cytokines, Kv1.3, Margatoxin, Salbutamol
Source:	Brain Research
ISSN:	0006-8993
Publisher:	Elsevier
Volume:	899
Number:	1-2
Page Range:	264-270
Date:	1 January 2001
PubMed:	View item in PubMed

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