Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro
Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro
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DOI：
10.1095/biolreprod67.2.668
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发表时间：
2002-08-01
影响因子：
3.6
通讯作者：
Rice, GE
中科院分区：
文献类型：
--
作者：
Lappas, M;Permezel, M;Rice, GE
促炎细胞因子参与人类分娩和分娩的启动和进展，特别是与感染诱导的早产有关。在非妊娠组织中，核因子κ B（NF-κ B）转录途径是促炎细胞因子释放的关键调节因子。在这些组织中，柳氮磺胺吡啶（SASP）通过其抑制NF-κ B活化的能力，抑制白细胞介素（IL）-2，IL-12和肿瘤坏死因子（TNF）-α的释放。因此，本研究的目的是调查是否NF-κ B激活调节促炎细胞因子在人类妊娠组织的形成。在不存在（对照）或存在SASP（0.1、1、5或10 mM）的情况下，将人胎盘、羊膜和绒毛膜蜕膜（n = 9个单独的胎盘）与10 μ g/ml脂多糖（LPS）孵育。孵育6 h后，收集组织，并通过电迁移率变动结合试验评估核提取物中的NF-κ B DNA结合活性。收集孵育培养基，并通过ELISA定量IL-6、IL-8和TNF-α的释放。用5 mM或更高浓度的SASP处理胎盘、羊膜和绒毛膜蜕膜显著抑制IL-6、IL-8和TNF-α的释放以及NF-κ B活化（ANOVA，P < 0.05）。本研究中提供的数据表明，NF-κ B转录途径是LPS刺激的IL-6、IL-8和TNF-α从人妊娠组织释放的关键调节因子。因此，控制NF-κ B的活化可能为减少感染相关性早产中促炎介质的释放提供一种替代治疗策略。
Proinflammatory cytokines are implicated in the initiation and progression of human labor and delivery, particularly in relation to infection-induced preterm labor. In nongestational tissues, the nuclear factor kappa B (NF-kappaB) transcription pathway is a key regulator of proinflammatory cytokine release. In these tissues, sulfasalazine (SASP), through its ability to inhibit NF-kappaB activation, inhibits release of interleukin (IL)-2, IL-12, and tumor necrosis factor (TNF)-alpha. Therefore, the aim of this study was to investigate whether or not NF-kappaB activation regulates the formation of proinflammatory cytokines in human gestational tissues. Human placenta, amnion, and choriodecidua (n = 9 separate placentas) were incubated with 10 mug/ml of lipopolysaccharide (LPS) in the absence (control) or presence of SASP (0.1, 1, 5, or 10 mM). After 6 h of incubation, the tissues were collected, and NF-kappaB DNA binding activity in nuclear extracts was assessed by electromobility shift binding assay. The incubation medium was collected and the release of IL-6, IL-8, and TNF-alpha was quantified by ELISA. Treatment of placenta, amnion, and choriodecidua with SASP at concentrations 5 mM or greater significantly inhibited the release of IL-6, IL-8, and TNF-alpha, and NF-kappaB activation (ANOVA, P < 0.05). The data presented in this study demonstrate that the NF-kappaB transcription pathway is a key regulator of LPS-stimulated IL-6, IL-8, and TNF-alpha release from human gestational tissues. The control of NF-kappaB activation may therefore provide an alternative therapeutic strategy for reducing the release of proinflammatory mediators in infection associated preterm labor.