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

Mami Noda, Yukihiro Kariura, Ulrike Pannasch, Kaori Nishikawa, Liping Wang, Toshihiro Seike, Masataka Ifuku, Yuki Kosai, Bing Wang, Christiane Nolte, Shunsuke Aoki, Helmut Kettenmann, Keiji Wada

Research output: Contribution to journalArticle

93 Citations (Scopus)

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-α) and interleukin-1β 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-α-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.

Original languageEnglish
Pages (from-to)397-410
Number of pages14
JournalJournal of Neurochemistry
Volume101
Issue number2
DOIs
Publication statusPublished - Apr 1 2007

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Microglia
Bradykinin
Bradykinin Receptors
Cytokines
Brain
Lipopolysaccharides
Receptors, Prostaglandin E, EP2 Subtype
Receptors, Prostaglandin E, EP4 Subtype
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Cyclooxygenase Inhibitors
Neurology
Neuroprotective Agents
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Coculture Techniques
Prostaglandins E
Interleukin-1
Dinoprostone
Neurons

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia. / Noda, Mami; Kariura, Yukihiro; Pannasch, Ulrike; Nishikawa, Kaori; Wang, Liping; Seike, Toshihiro; Ifuku, Masataka; Kosai, Yuki; Wang, Bing; Nolte, Christiane; Aoki, Shunsuke; Kettenmann, Helmut; Wada, Keiji.

In: Journal of Neurochemistry, Vol. 101, No. 2, 01.04.2007, p. 397-410.

Research output: Contribution to journalArticle

Noda, M, Kariura, Y, Pannasch, U, Nishikawa, K, Wang, L, Seike, T, Ifuku, M, Kosai, Y, Wang, B, Nolte, C, Aoki, S, Kettenmann, H & Wada, K 2007, 'Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia', Journal of Neurochemistry, vol. 101, no. 2, pp. 397-410. https://doi.org/10.1111/j.1471-4159.2006.04339.x
Noda, Mami ; Kariura, Yukihiro ; Pannasch, Ulrike ; Nishikawa, Kaori ; Wang, Liping ; Seike, Toshihiro ; Ifuku, Masataka ; Kosai, Yuki ; Wang, Bing ; Nolte, Christiane ; Aoki, Shunsuke ; Kettenmann, Helmut ; Wada, Keiji. / Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia. In: Journal of Neurochemistry. 2007 ; Vol. 101, No. 2. pp. 397-410.
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