Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia
Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia
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DOI：
10.1111/j.1471-4159.2006.04339.x
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发表时间：
2007-04-01
影响因子：
4.7
通讯作者：
Wada, Keiji
中科院分区：
文献类型：
--
作者：
Noda, Mami;Kariura, Yukihiro;Wada, Keiji
缓激肽（BK）是急性脑损伤的介质。BK受体已在小胶质细胞（大脑的病理传感器）上被鉴定。在这里，我们报告说，BK衰减脂多糖（LPS）诱导的释放肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β的小胶质细胞，从而作为一种抗炎介质在大脑中。这种作用通过提高细胞内cAMP或刺激前列腺素受体EP 2和EP 4来模拟，而cAMP拮抗剂、前列腺素受体拮抗剂或诱导型环氧合酶（环氧合酶-2）抑制剂则可消除这种作用。BK还促进前列腺素E-2的形成和微粒体前列腺素E合成酶的表达。BK受体和EP 2/EP 4受体的表达也增强。使用生理技术，我们确定了功能BK受体不仅在文化，但也在小胶质细胞从急性脑切片。BK减少LPS诱导的神经元-小胶质细胞共培养物中的神经元死亡。这可能是通过小胶质细胞介导的，因为它不影响纯神经元培养物中TNF-α诱导的神经元死亡。我们的数据表明BK通过调节小胶质细胞功能在中枢神经系统中具有抗炎和神经保护作用。
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-1 beta 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 E-2 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.