...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacogenomics >Decreased sigmoidal ABCB1 (P-glycoprotein) expression in ulcerative colitis is associated with disease activity
【24h】

Decreased sigmoidal ABCB1 (P-glycoprotein) expression in ulcerative colitis is associated with disease activity

机译：溃疡性结肠炎中乙状结肠ABCB1（P-糖蛋白）表达降低与疾病活动相关

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Aims: The modulation of the intestinal expression of detoxifying proteins by relevant transcription factors, intracellular receptors and cytokines in ulcerative colitis (UC) is poorly understood. Here, we compared the intestinal expression of drug transporters, metabolizing enzymes and putative regulatory genes between inflamed and noninflamed tissue and studied their modulation by disease activity. Materials & methods: Sigmoidal biopsies of 18 UC patients and 18 healthy volunteers matched for age, gender and ABCB1 3435C>T genotype were investigated for mRNA expression levels of 43 systematically selected candidate genes by low-density array real-time PCR. Additionally, the ABCB1 gene product P-glycoprotein was visualized by immunohistochemistry and quantified by western blotting. Disease phenotype was categorized by clinical, endoscopic and histopathological examination. Disease activity was quantified by clinical activity index. Results: In inflamed sigmoidal tissue from UC patients, 11 genes (NAT1, NR2B1, CEBPB, IFG, IL8, IL10, S100A12, SPP1, DEFA5, DEFA6 and HAMP) were overexpressed. By contrast, only the major human efflux transporter ABCB1 showed significantly lower expression levels, that were inversely correlated with those of certain antimicrobial peptides (DEFA5/6) and cytokines (IL1β and IL8). Cell culture experiments revealed a time-dependent decrease of ABCB1 expression upon IL8 exposure. Disease activity profoundly modified ABCB1 expression, indicated by an inverse correlation of clinical activity index values with ABCB1 mRNA expression (r = -0.603; p = 0.017) and markedly reduced protein expression in UC patients with moderate and severe symptomology (p = 0.011). Conclusion: Cytokine-mediated downregulation of the major human efflux transporter ABCB1 in inflamed intestine of UC patients is presumably dependent on disease activity, with a possible contribution from IL8.
机译：目的：了解溃疡性结肠炎（UC）中相关转录因子，细胞内受体和细胞因子对解毒蛋白肠表达的调节作用。在这里，我们比较了发炎和未发炎组织之间药物转运蛋白，代谢酶和推定的调节基因在肠道中的表达，并研究了疾病活动对它们的调节作用。材料与方法：通过低密度阵列实时荧光定量PCR，对年龄，性别和ABCB1 3435C> T基因型相匹配的18例UC患者和18例健康志愿者的乙状结肠活检进行了研究，以调查43种系统选择的候选基因的mRNA表达水平。另外，通过免疫组织化学使ABCB1基因产物P-糖蛋白可视化，并通过蛋白质印迹法定量。通过临床，内窥镜检查和组织病理学检查将疾病表型分类。通过临床活动指数定量疾病活动。结果：在来自UC患者的乙状结肠发炎组织中，11个基因（NAT1，NR2B1，CEBPB，IFG，IL8，IL10，S100A12，SPP1，DEFA5，DEFA6和HAMP）过表达。相比之下，只有主要的人类外排转运蛋白ABCB1表现出明显较低的表达水平，与某些抗菌肽（DEFA5 / 6）和细胞因子（IL1β和IL8）的表达水平呈负相关。细胞培养实验表明，IL8暴露后ABCB1表达随时间的下降。在具有中度和重度症状的UC患者中，疾病活动极大地改变了ABCB1表达，临床活性指标值与ABCB1 mRNA表达呈负相关（r = -0.603； p = 0.017），并且蛋白表达显着降低（p = 0.011）。结论：细胞因子介导的UC患者发炎肠道中主要的人外源转运蛋白ABCB1的下调可能取决于疾病的活动，IL8可能对此做出了贡献。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号