改变的PGE2-EP2与HBV相关的急性慢性肝衰竭中的过度免疫应答相

StephenW

Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure

    Yunyun Wang†, Chao Chen†, Jinjin Qi, Fengtian Wu, Jun Guan, Zhi ChenEmail author and Haihong ZhuEmail author

†Contributed equally
Journal of Translational Medicine201917:93

https://doi.org/10.1186/s12967-019-1844-0

©  The Author(s) 2019

    Received: 28 October 2018Accepted: 11 March 2019Published: 19 March 2019

Abstract
Background and aims

Prostaglandin E receptor 2 (EP2) is an immune modulatory molecule that regulates the balance of immunity. Here we investigated the role of EP2 in immune dysregulation in patients with acute-on-chronic liver failure (ACLF).
Methods

Plasma Progstaglandin E2 (PGE2) levels and EP2 expression on immune cells were determined in blood samples collected from patients with chronic hepatitis B related ACLF(HB-ACLF), patients with chronic hepatitis B (CHB), acute decompensated cirrhosis without ACLF (AD) and healthy controls (HC). Cytokine production, bacterial phagocytosis and reactive oxygen species (ROS) production were detected to explore the role of EP2 in regulating immune cell functions.
Results

The plasma PGE2 levels were increased and EP2 expression on CD8+ T cells was decreased in HB-ACLF compared with those in controls. The levels of PGE2 and EP2 were associated with systemic inflammation and disease severity. Small molecular chemicals against EP2 increased both cytokine secretion in PBMCs and ROS production in neutrophils and monocytes, but decreased monocytic phagocytosis. By contrast, an EP2-selective agonist reduced the production of a series of cytokines in PBMCs, but increased G-CSF.
Conclusion

Altered PGE2-EP2 augmented the excessive inflammation of innate and adaptive immune cells in response to LPS or E. coli in HB-ACLF. EP2 might be a new potential target for HB-ACLF treatment.
Keywords

    ACLF
    PGE2
    EP2
    Systemic inflammation

StephenW

改变的PGE2-EP2与HBV相关的急性慢性肝衰竭中的过度免疫应答相关

    王云云†，陈超†，齐金进，吴凤田，关俊君，陈志，电子书作者，朱海海作者

†同等贡献
Journal of Translational Medicine201917：93

https://doi.org/10.1186/s12967-019-1844-0

©作者2019

    收稿日期：2018年10月28日接受日期：2019年3月11日出版日期：2019年3月19日

抽象
背景和目标

前列腺素E受体2（EP2）是一种调节免疫平衡的免疫调节分子。在这里，我们调查了EP2在急性慢性肝衰竭（ACLF）患者免疫失调中的作用。
方法

从慢性乙型肝炎相关ACLF（HB-ACLF），慢性乙型肝炎（CHB），无ACLF（AD）的急性失代偿性肝硬化患者采集的血液样本中测定血浆Progstaglandin E2（PGE2）水平和EP2在免疫细胞中的表达和健康对照（HC）。检测细胞因子产生，细菌吞噬作用和活性氧（ROS）产生，以探索EP2在调节免疫细胞功能中的作用。
结果

与对照组相比，HB-ACLF中血浆PGE2水平升高，CD8 + T细胞上EP2表达降低。 PGE2和EP2的水平与全身性炎症和疾病严重程度相关。针对EP2的小分子化学物质增加了PBMC中的细胞因子分泌和中性粒细胞和单核细胞中的ROS产生，但是减少了单核细胞的吞噬作用。相比之下，EP2选择性激动剂减少了PBMC中一系列细胞因子的产生，但增加了G-CSF。
结论

改变的PGE2-EP2增强了先天性和适应性免疫细胞的过度炎症，以响应HB-ACLF中的LPS或大肠杆菌。 EP2可能是HB-ACLF治疗的新潜在目标。
关键词

    ACLF
    PGE2
    EP2
    全身性炎症

StephenW

https://translational-medicine.b ... 6/s12967-019-1844-0

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