Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure
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 a...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-03-01
|
Series: | Journal of Translational Medicine |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12967-019-1844-0 |
id |
doaj-cf3742559b324da685ea1d2ba80291e8 |
---|---|
record_format |
Article |
spelling |
doaj-cf3742559b324da685ea1d2ba80291e82020-11-25T02:07:44ZengBMCJournal of Translational Medicine1479-58762019-03-0117111410.1186/s12967-019-1844-0Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failureYunyun Wang0Chao Chen1Jinjin Qi2Fengtian Wu3Jun Guan4Zhi Chen5Haihong Zhu6State 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityAbstract 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.http://link.springer.com/article/10.1186/s12967-019-1844-0ACLFPGE2EP2Systemic inflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yunyun Wang Chao Chen Jinjin Qi Fengtian Wu Jun Guan Zhi Chen Haihong Zhu |
spellingShingle |
Yunyun Wang Chao Chen Jinjin Qi Fengtian Wu Jun Guan Zhi Chen Haihong Zhu Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure Journal of Translational Medicine ACLF PGE2 EP2 Systemic inflammation |
author_facet |
Yunyun Wang Chao Chen Jinjin Qi Fengtian Wu Jun Guan Zhi Chen Haihong Zhu |
author_sort |
Yunyun Wang |
title |
Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure |
title_short |
Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure |
title_full |
Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure |
title_fullStr |
Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure |
title_full_unstemmed |
Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure |
title_sort |
altered pge2-ep2 is associated with an excessive immune response in hbv-related acute-on-chronic liver failure |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2019-03-01 |
description |
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. |
topic |
ACLF PGE2 EP2 Systemic inflammation |
url |
http://link.springer.com/article/10.1186/s12967-019-1844-0 |
work_keys_str_mv |
AT yunyunwang alteredpge2ep2isassociatedwithanexcessiveimmuneresponseinhbvrelatedacuteonchronicliverfailure AT chaochen alteredpge2ep2isassociatedwithanexcessiveimmuneresponseinhbvrelatedacuteonchronicliverfailure AT jinjinqi alteredpge2ep2isassociatedwithanexcessiveimmuneresponseinhbvrelatedacuteonchronicliverfailure AT fengtianwu alteredpge2ep2isassociatedwithanexcessiveimmuneresponseinhbvrelatedacuteonchronicliverfailure AT junguan alteredpge2ep2isassociatedwithanexcessiveimmuneresponseinhbvrelatedacuteonchronicliverfailure AT zhichen alteredpge2ep2isassociatedwithanexcessiveimmuneresponseinhbvrelatedacuteonchronicliverfailure AT haihongzhu alteredpge2ep2isassociatedwithanexcessiveimmuneresponseinhbvrelatedacuteonchronicliverfailure |
_version_ |
1724929956785422336 |