...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A
【24h】

Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A

机译：树突状细胞中白介素23的产生受蛋白磷酸酶2A的负调控

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

IL-12 and IL-23 are produced by activated antigen-presenting cells but the two induce distinct immune responses by promoting Th1 and Th17 cell differentiation, respectively. IL-23 is a heterodimeric cyto-kine consisting of two subunits: p40 that is shared with IL-12 and p19 unique to IL-23. In this study, we showed that the production of IL-23 but not IL-12 was negatively regulated by protein phosphatase 2A (PP2A) in dendritic cells (DC). PP2A inhibits IL-23 production by suppressing the expression of the IL-23p19 gene. Treating DC with okadaic acid that inhibits the PP2A activity or knocking down the catalytic subunit of PP2A with siRNA enhanced IL-23 but not IL-12 production. Unlike PPM, MAP kinase phosphatase-1 or CYLD did not show an effect on IL-23 production supporting the specificity of PP2A. PP2A-mediated inhibition requires a newly made protein that is likely responsible for bringing PP2A and IKKβ together upon LPS stimulation, which then results in the termination of IKK phosphorylation. Thus, our results uncovered an important role of the protein phosphatase in the regulation of IL-23 production and identified PP2A as a previously uncharacterized inhibitor of IL-23p19 expression in DC.
机译：IL-12和IL-23由活化的抗原呈递细胞产生，但二者分别通过促进Th1和Th17细胞分化诱导不同的免疫反应。 IL-23是由两个亚基组成的异二聚体细胞因子：与IL-12共享的p40和IL-23独有的p19。在这项研究中，我们显示树突状细胞（DC）中的蛋白磷酸酶2A（PP2A）负调控IL-23的产生，而IL-12则不受到负调控。 PP2A通过抑制IL-23p19基因的表达来抑制IL-23的产生。用抑制PP2A活性的冈田酸处理DC或用siRNA敲低PP2A的催化亚基可增强IL-23的产生，但不能增强IL-12的产生。与PPM不同，MAP激酶磷酸酶-1或CYLD对IL-23的产生没有显示出支持PP2A特异性的作用。 PP2A介导的抑制作用需要一种新产生的蛋白质，该蛋白质可能在LPS刺激后将PP2A和IKKβ结合在一起，从而导致IKK磷酸化终止。因此，我们的研究结果揭示了蛋白磷酸酶在调节IL-23产生中的重要作用，并将PP2A鉴定为DC中IL-23p19表达的先前未知的抑制剂。

著录项

  • 来源
  • 作者

    JiHoon Chang; Timothy J. Voorhees; Yusen Liu; Yongge Zhao; Cheong-Hee Chang;

  • 作者单位

    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109;

    rnDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109;

    rnCenter for Perinatal Research, Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH 43205;

    rnLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20817;

    rnDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cytokine; NF-κB; TLR;

    机译：细胞因子NF-κB;TLR;

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