State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Shangcheng District, Hangzhou, 310003, Zhejiang, China.
J Transl Med. 2019 Mar 19;17(1):93. doi: 10.1186/s12967-019-1844-0.
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).
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.
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.
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.
前列腺素 E 受体 2（EP2）是一种免疫调节分子，可调节免疫平衡。在此，我们研究了 EP2 在慢性乙型肝炎相关慢加急性肝衰竭（HB-ACLF）患者免疫失调中的作用。
收集慢性乙型肝炎相关 ACLF（HB-ACLF）、慢性乙型肝炎（CHB）、无 ACLF 的急性失代偿性肝硬化（AD）和健康对照（HC）患者的血液样本，检测血浆前列腺素 E2（PGE2）水平和免疫细胞上的 EP2 表达。检测细胞因子产生、细菌吞噬和活性氧（ROS）产生，以探索 EP2 在调节免疫细胞功能中的作用。
与对照组相比，HB-ACLF 患者血浆 PGE2 水平升高，CD8 T 细胞上的 EP2 表达降低。PGE2 和 EP2 水平与全身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 PBMCs 中的细胞因子分泌和中性粒细胞和单核细胞中的 ROS 产生，但降低了单核细胞吞噬作用。相比之下，EP2 选择性激动剂减少了 PBMCs 中一系列细胞因子的产生，但增加了 G-CSF。
改变的 PGE2-EP2 增强了 HB-ACLF 中固有和适应性免疫细胞对 LPS 或大肠杆菌的过度炎症反应。EP2 可能是 HB-ACLF 治疗的一个新的潜在靶点。
