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

作者：Yunyun Wang, Chao Chen, Jinjin Qi, Fengtian Wu, Jun Guan, Zhi Chen, Haihong Zhu · 发表于：Journal of Translational Medicine · 年份：2019 · DOI：10.1186/s12967-019-1844-0 · 被引用次数：18 · 研究领域：Inflammatory mediators and NSAID effects、Immune Response and Inflammation、Drug-Induced Hepatotoxicity and Protection

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: 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.