Lidocaine inhibits epithelial chemokine secretion via inhibition of nuclear factor κB activation
Lidocaine inhibits epithelial chemokine secretion via inhibition of nuclear factor κB activation
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DOI：
10.1016/j.imbio.2009.05.006
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发表时间：
2010-04-01
期刊：
影响因子：
2.8
通讯作者：
Chowers, Yehuda
中科院分区：
文献类型：
--
作者：
Lang, Alon;Ben Horin, Shomron;Chowers, Yehuda
目的：研究利多卡因对肠上皮细胞的抗炎作用。方法：在体外培养的HT-29和T-84细胞中加入肿瘤坏死因子-α、利多卡因、乌头碱和藜芦碱。用酶联免疫吸附试验检测IL-8和IP-10的分泌。用基因芯片检测基因表达。用实时荧光定量聚合酶链式反应(Real-time PCR)对结果进行验证。结果：利多卡因可抑制IL-8和IP-10的自发分泌和肿瘤坏死因子-α诱导的分泌。藜芦碱或乌头碱、电压门控性钠通道(VGSC)激动剂与利多卡因的结合并不改变利多卡因对细胞因子分泌的影响。基因芯片分析表明，I-kappa B转录受肿瘤坏死因子-α诱导，利多卡因抑制。I kappa B实时定量聚合酶链式反应证实了这一观察结果。Western印迹分析表明，利多卡因可显著抑制TNE-α处理后I kappa B的降解。结论：利多卡因可抑制肠上皮细胞分泌IL-8和IP-10。这种作用是通过降低I kappaB的磷酸化来抑制核因子kappaB的激活而实现的，而不是通过利多卡因对VGSC的作用来实现的。(C)2009年爱思唯尔股份有限公司。版权所有。
Aim: To study the antiinflammatory effect of lidocaine in intestinal epithelial cells.Methods: HT-29 and T-84 cells were grown in culture with and without TNF-alpha, lidocaine, aconitine and veratridine. The secretion of IL-8 and IP-10 was measured by ELISA. A cDNA microarray was used to assess gene expression. Real-time PCR was used to confirm the results. Western blots and a modified electromobility shift assay (EMSA) were used to assess NE kappa B activation.Results: Lidocaine inhibited spontaneous and TNF-alpha induced secretion of IL-8 and IP-10. The combination of veratridine or aconitine, voltage-gated sodium channels (VGSC) agonists that open VGSCs, with lidocaine did not alter the effect of lidocaine on cytokine secretion. Gene array analysis revealed that I kappa B transcription was induced by TNF-alpha and inhibited by lidocaine. I kappa B real-time PCR confirmed this observation. A Western blot analysis demonstrated that the degradation of I kappa B following TNE-alpha treatment was markedly inhibited by lidocaine. Lidocaine treatment resulted in decreased generation of phosphorylated I kappa B. A modified EMSA was complementary and demonstrated marked inhibition of NF kappa B nuclear binding.Conclusion: Lidocaine inhibits IL-8 and IP-10 secretion from intestinal cells. This effect is mediated by inhibition of NF kappa B activation via decreased I kappa B phosphorylation and is not mediated by lidocaine's effect on VGSC. (C) 2009 Elsevier GmbH. All rights reserved.