激活β肾上腺素受体(2)防止志贺毒素2-induced tnf基因转录。
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中村,约翰EJ, Imaizumi Yanagawa Y, Kohsaka T
激活β肾上腺素受体(2)防止志贺毒素2-induced tnf基因转录。
J是Soc Nephrol。2001年11月,12 (11):2288 - 99。
- PubMed ID
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11675405 (在PubMed]
- 文摘
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暴露的肾小管上皮细胞志贺毒素2 (Stx-2)引起细胞毒性,这种毒素的潜能是增强的肿瘤坏死因子-α(tnf)。它已经表明Stx-2诱发tnf生产和激活的β(2)-adrenoceptors会使tnf。然而,对β的信号通路(2)肾上腺素能受体受体激动剂抑制Stx-2-induced tnf基因转录。可能信号组件参与这个途径。人类adenocarcinoma-derived肾小管上皮细胞(ACHN)暴露在Stx-2存在与否的β肾上腺素能受体受体激动剂(2)。增殖蛋白激酶(MAPK),激活蛋白1 (AP-1)和核factor-kappa B (nf -κB)测量评估tnf基因转录的调控机制。Stx-2 (4 pg / ml)刺激MAPK(第42页/ p44 p38)和AP-1和tnf子活动增加了2.4倍。tnf的增加减了两页/ p44抑制剂,PD098059 (10 (6) M),和p38抑制剂,SB203580 (10 (6) M),和AP-1-binding活动被PD098059抑制。特布他林(10(6)到10 (8)M)抑制MAPK(第42页/ p44 p38), nf -κB (p50 p65)和tnf推广活动在剂量依赖性的方式阻止了β肾上腺素能受体拮抗剂(2),ICI118,551。然而,抑制MAPK(第42页/ p44)和tnf子活动被cAMP-protein部分阻止激酶(PKA)抑制剂,h - 89 (5 x 10(6)米)和KT5720(10(5)米),而抑制p38 MAPK和nf -κB (p50)并没有被这些抑制剂。 The suppression of NF-kappa B (p65) was completely overcome by H-89 or KT5720. In summary, the downregulation of TNF-alpha transcription by terbutaline was mediated by an inhibitory effect of beta(2)-adrenoceptor activation on MAPK (p42/p44, p38) and NF-kappa B (p50/p65), which were exerted through a cAMP-PKA pathway and a cAMP-independent mechanism. It is likely that cAMP-PKA and MAPK (p42/p44, p38) may play a critical role in the regulation of the Stx-2-induced TNF-alpha transcription via beta(2)-adrenoceptor activation.