Identifying Prokineticin2 as a Novel Immunomodulatory Factor in Diagnosis and Treatment of Sepsis*

作者全名:"Yu, Xiaoyan; Chen, Jingyi; Tang, Hong; Tu, Qianqian; Li, Yue; Yuan, Xi; Zhang, Xuemei; Cao, Ju; Molloy, David Paul; Yin, Yibing; Chen, Dapeng; Song, Zhixin; Xu, Pingyong"

作者地址:"[Yu, Xiaoyan; Chen, Jingyi; Tu, Qianqian; Yuan, Xi; Chen, Dapeng; Song, Zhixin; Xu, Pingyong] Chongqing Med Univ, Dept Clin Lab,Chongqing Key Lab Child Infect & Im, Childrens Hosp,Key Lab Child Dev & Disorders, Natl Clin Res Ctr Child Hlth & Disorders,Minist E, Chongqing, Peoples R China; [Tang, Hong] Chongqing Med Univ, Dept Crit Care Med, Dept Surg Intens Care Unit, Affiliated Hosp 1, Chongqing, Peoples R China; [Li, Yue] Chongqing Med Univ, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing, Peoples R China; [Zhang, Xuemei; Yin, Yibing] Chongqing Med Univ, Dept Lab Med, Key Lab Diagnost Med, Chongqing, Peoples R China; [Cao, Ju] Chongqing Med Univ, Dept Lab Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Molloy, David Paul] ChongQing Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, Chongqing, Peoples R China; [Xu, Pingyong] Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Key Lab RNA Biol,Natl Lab Biomacromol, Beijing, Peoples R China; [Xu, Pingyong] Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China"

通信作者:"Chen, DP; Song, ZX (通讯作者),Chongqing Med Univ, Dept Clin Lab,Chongqing Key Lab Child Infect & Im, Childrens Hosp,Key Lab Child Dev & Disorders, Natl Clin Res Ctr Child Hlth & Disorders,Minist E, Chongqing, Peoples R China."

来源:CRITICAL CARE MEDICINE

ESI学科分类:CLINICAL MEDICINE

WOS号:WOS:000771070100035

JCR分区:Q1

影响因子:8.8

年份:2022

卷号:50

期号:4

开始页:674

结束页:684

文献类型:Article

关键词:immunoregulation; macrophage; prokineticin2; sepsis

摘要:"OBJECTIVES: Sepsis remains a highly lethal disease, whereas the precise reasons for death remain poorly understood. Prokineticin2 is a secreted protein that regulates diverse biological processes. Whether prokineticin2 is beneficial or deleterious to sepsis and the underlying mechanisms remain unknown. DESIGN: Prospective randomized animal investigation and in vitro studies. SETTING: Research laboratory at a medical university hospital. SUBJECTS: Prokineticin2 deficiency and wild-type C57BL/6 mice were used for in vivo studies; sepsis patients by Sepsis-3 definitions, patient controls, and healthy controls were used to obtain blood for in vitro studies. INTERVENTIONS: Prokineticin2 concentrations were measured and analyzed in human septic patients, patient controls, and healthy individuals. The effects of prokineticin2 on sepsis-related survival, bacterial burden, organ injury, and inflammation were assessed in an animal model of cecal ligation and puncture-induced polymicrobial sepsis. In vitro cell models were also used to study the role of prokineticin2 on antibacterial response of macrophages. MEASUREMENTS AND MAIN RESULTS: Prokineticin2 concentration is dramatically decreased in the patients with sepsis and septic shock compared with those of patient controls and healthy controls. Furthermore, the prokineticin2 concentration in these patients died of sepsis or septic shock is significantly lower than those survival patients with sepsis or septic shock, indicating the potential value of prokineticin2 in the diagnosis of sepsis and septic shock, as well as the potential value in predicting mortality in adult patients with sepsis and septic shock. In animal model, recombinant prokineticin2 administration protected against sepsis-related deaths in both heterozygous prokineticin2 deficient mice and wild-type mice and alleviated sepsis-induced multiple organ damage. In in vitro cell models, prokineticin2 enhanced the phagocytic and bactericidal functions of macrophage through signal transducers and activators of transcription 3 pathway which could be abolished by signal transducers and activators of transcription 3 inhibitors S3I-201. Depletion of macrophages reversed prokineticin2-mediated protection against polymicrobial sepsis. CONCLUSIONS: This study elucidated a previously unrecognized role of prokineticin2 in clinical diagnosis and treatment of sepsis. The proof-of-concept study determined a central role of prokineticin2 in alleviating sepsis-induced death by regulation of macrophage function, which presents a new strategy for sepsis immunotherapy."

基金机构:National Natural Science Foundation of China [81801956]; General Clinical Research Project of National Center for Clinical Medicine of Children's Health and Disease; Children's Hospital of Chongqing Medical University [NCRC2019-GP-14]; Chongqing Science and Technology Commission [cstc2018jcyjAX0780]; Distinguished Young Scholars of the Children's Hospital of Chongqing Medical University

基金资助正文:"Supported, in part, by the National Natural Science Foundation of China (Grant Number: 81801956 to Dr. Song), General Clinical Research Project of National Center for Clinical Medicine of Children's Health and Disease, the Children's Hospital of Chongqing Medical University (Grant Number: NCRC2019-GP-14 to Dr. Song), Chongqing Science and Technology Commission (Grant Number: cstc2018jcyjAX0780 to Dr. Chen), and Distinguished Young Scholars of the Children's Hospital of Chongqing Medical University (to Dr. Song)."