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

Item Type:Article
Title:Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia
Creators Name:Noda, M. and Kariura, Y. and Pannasch, U. and Nishikawa, C. and Wang, L. and Seike, T. and Ifuku, M. and Kosai, Y. and Wang, B. and Nolte, C. and Aoki, S. and 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 neuron–microglia 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
Publisher:Blackwell Publishing
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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