Lipopolysaccharide activates the kallikrein–kinin system in mouse choroid plexus cell line ECPC4
Lipopolysaccharide activates the kallikrein–kinin system in mouse choroid plexus cell line ECPC4
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DOI：
10.1016/j.neulet.2008.01.072
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发表时间：
2008-04
影响因子：
2.5
通讯作者：
M. Takano;Chieko Satoh;Naomi Kunimatsu;M. Otani;M. Hamada-Kanazawa;M. Miyake;KyongSong Ming;K. Yayama;H. Okamoto
中科院分区：
文献类型：
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作者：
M. Takano;Chieko Satoh;Naomi Kunimatsu;M. Otani;M. Hamada-Kanazawa;M. Miyake;KyongSong Ming;K. Yayama;H. Okamoto
激肽释放酶-激肽系统在脑炎症中的调节仍不清楚。在这里，我们使用逆转录聚合酶链反应（RT-PCR）技术表明，脂多糖（LPS）激活激肽释放酶-激肽系统，通过增强缓激肽（BK）的释放，并改变激肽释放酶-激肽系统组件的mRNA水平，包括高分子量（H-）和低分子量（L-）激肽原，在ECPC 4细胞，小鼠脉络丛上皮细胞系。LPS处理增加了ECPC 4细胞上清中免疫反应性缓激肽的释放，向培养物中添加LPS（500 ng/ml）导致ECPC 4细胞中H-和L-激肽原mRNA水平在24- 48小时内升高。此外，脂多糖处理后4小时内缓激肽2型和1型受体mRNA水平升高，但没有改变组织激肽释放酶或血浆激肽释放酶mRNA水平。另一方面，在加入LPS至ECPC 4细胞后4-8h内，促炎介质白细胞介素-1 β（IL-1β）、肿瘤坏死因子-α（TNF-α）和环氧合酶-2 mRNA的表达增加。加入IL-1β和TNF-α以研究ECPC 4细胞中激肽原表达的主要介质，显著诱导ECPC 4细胞中H-和L-激肽原mRNA的表达。这些结果表明，LPS通过自分泌诱导IL-1β和TNF-α激活脉络丛中的激肽释放酶-激肽系统。
Regulation of the kallikrein–kinin system in cerebral inflammation is still unclear. Here, we used reverse-transcription polymerase chain reaction (RT-PCR) techniques to show that lipopolysaccharide (LPS) activates the kallikrein–kinin system by enhancing liberation of bradykinin (BK), and alters mRNA levels of kallikrein–kinin system components, including high molecular weight (H-) and low molecular weight (L-) kininogens, in ECPC4 cells, a cell line of mouse choroid plexus epithelium. LPS treatment increased liberation of immunoreactive bradykinin in the supernatant of ECPC4 cells, and addition of LPS (500ng/ml) to cultures resulted in elevation of H- and L-kininogen mRNA levels in ECPC4 cells within 24–48h. Furthermore, LPS treatment elevated bradykinin type 2 and type 1 receptor mRNA levels within 4h, but did not change tissue kallikrein or plasma kallikrein mRNA levels. On the other hand, expression of pro-inflammatory mediators interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 mRNA increased within 4–8h after addition of LPS to ECPC4 cells. The addition of IL-1β and TNF-α to investigate the major mediator for kininogen expression in ECPC4 cells remarkably induced expression of H- and L-kininogen mRNAs in ECPC4 cells. These results suggest that LPS activates the kallikrein–kinin system in the choroid plexus via autocrine induction of IL-1β and TNF-α.