Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia

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Item Type:	Article
Title:	Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia
Creators Name:	Noda, M., Kariura, Y., Pannasch, U., Nishikawa, C., Wang, L., Seike, T., Ifuku, M., Kosai, Y., Wang, B., Nolte, C., Aoki, S., Kettenmann, H. and Wada, K.
Abstract:	Bradykinin (BK) has been reported to be a mediator of brain damage in acute insults. Receptors for BK have been identified on microglia, the pathologic sensors of the brain. Here, we report that BK attenuated lipopolysaccharide (LPS)-induced release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta from microglial cells, thus acting as an anti-inflammatory mediator in the brain. This effect was mimicked by raising intracellular cAMP or stimulating the prostanoid receptors EP2 and EP4, while it was abolished by a cAMP antagonist, a prostanoid receptor antagonist, or by an inhibitor of the inducible cyclooxygenase (cyclooxygenase-2). BK also enhanced formation of prostaglandin E2 and expression of microsomal prostaglandin E synthase. Expression of BK receptors and EP2/EP4 receptors were also enhanced. Using physiological techniques, we identified functional BK receptors not only in culture, but also in microglia from acute brain slices. BK reduced LPS-induced neuronal death in neuronmicroglia co-cultures. This was probably mediated via microglia as it did not affect TNF-alpha-induced neuronal death in pure neuronal cultures. Our data imply that BK has anti-inflammatory and neuroprotective effects in the central nervous system by modulating microglial function.
Keywords:	Bradykinin, Lipopolysaccharide, Microglia, Prostaglandin, Tumor necrosis factor-alpha, Animals, Mice, Rats
Source:	Journal of Neurochemistry
ISSN:	0022-3042
Publisher:	Blackwell Publishing
Volume:	101
Number:	2
Page Range:	397-410
Date:	April 2007
Official Publication:	https://doi.org/10.1111/j.1471-4159.2006.04339.x
PubMed:	View item in PubMed

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