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Phosphorylated Hsp27 prevents LPS‐induced excessive inflammation in THP‐1 cells via suppressing ROS‐mediated upregulation of CBP

机译:磷酸化的HSP27通过抑制ROS介导的CBP介导的ROS介导的CBP,防止LPS引起的过量炎症

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摘要

Abstract Heat shock protein 27 (Hsp27) is a member of the small heat shock protein family expressed at high levels to protect cells against heat shock and other conditions of stress. Hsp27 has been indicated in the regulation of inflammation signaling pathway, and Hsp27 phosphorylation is vital for efficient control of host‐defense response in early stages of lipopolysaccharide (LPS)‐stimulated inflammation. The notion that CREB‐binding protein (CBP) is involved in the regulation of two major transcription factors, nuclear factor‐κB (NF‐κB) and AP‐1, suggests that CBP, as a coactivator protein, may also play an important role in the cellular response to inflammation. Here, we explored the mechanism underlying the regulatory relationships between Hsp27 and CBP in THP‐1 cells, and found that phosphorylated Hsp27 was critical to the protein level of CBP. Furthermore, in exploring the signaling mechanisms underlying its action, we found that p38MAPK‐MK2‐Hsp27 regulated NF‐κB via CBP, which acted as a multi‐protein complex assembly scaffold. Finally, we demonstrated that phosphorylated Hsp27 reduced reactive oxygen species accumulation thereby significantly repressed LPS‐induced excessive increase of CBP. Taken together, our data demonstrated that Hsp27, in its phosphorylation state, plays a critical role in controlling LPS‐induced inflammatory response by modulating CBP.
机译:摘要热休克蛋白27(Hsp27)是热休克蛋白家族中的一员,在高水平表达,以保护细胞免受热休克和其他应激条件的影响。Hsp27已被证实参与炎症信号通路的调节,并且在脂多糖(LPS)刺激炎症的早期阶段,Hsp27磷酸化对于有效控制宿主防御反应至关重要。CREB结合蛋白(CBP)参与两种主要转录因子核因子-κB(NF-κB)和AP-1的调节,这表明CBP作为一种共激活蛋白,也可能在细胞对炎症的反应中发挥重要作用。在这里,我们探索了Hsp27和CBP在THP-1细胞中调节关系的机制,发现磷酸化的Hsp27对CBP的蛋白质水平至关重要。此外,在探索其作用的信号机制时,我们发现p38MAPK‐MK2‐Hsp27通过CBP调节NF‐κB,CBP是一种多蛋白复合物组装支架。最后,我们证明磷酸化Hsp27减少活性氧的积累,从而显著抑制LPS诱导的CBP过度增加。综上所述,我们的数据表明,处于磷酸化状态的Hsp27通过调节CBP在控制LPS诱导的炎症反应中起着关键作用。

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  • 来源
    《Cell biology international.》 |2020年第1期|共15页
  • 作者单位

    Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology College of Life;

    Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology College of Life;

    Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology College of Life;

    State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing;

    Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology College of Life;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    CBP; Hsp27; inflammatory responses; MAPKs; NF‐κB; ROS;

    机译:CBP;HSP27;炎症反应;MAPKS;NF-κB;ROS;

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