PMID- 32793229
OWN - NLM
STAT- MEDLINE
DCOM- 20210420
LR  - 20210420
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - 17beta-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating 
      Nucleus Translocation of RelB.
PG  - 1591
LID - 10.3389/fimmu.2020.01591 [doi]
LID - 1591
AB  - Sepsis is more common among males than females, and the unequal estrogen levels 
      have been suspected to play a vital role in gender differences. Recently, trained 
      immunity is reported to be a novel strategy for the innate immune system to fight 
      infection. However, it has not been clarified whether beta-glucan-induced trained 
      immunity causes different responses to early sepsis between male and female mice. 
      In this study, sepsis was induced in mice by intraperitoneal injection of 
      Escherichia coli (E. coli). The changes of inflammatory cytokines expression, and 
      macrophage polarization in male, female, and ovariectomized C57BL/6 mice in 
      sepsis model were investigated. For in vitro studies, different macrophages were 
      treated with LPS. The function of estradiol (E2) on macrophage cell lines was 
      verified and the mechanism of E2 affecting trained immunity was explored. We 
      demonstrated that beta-glucan-induced trained immunity was more resistant to sepsis 
      in female than male mice. Macrophage polarization toward the M1 phenotype, which 
      exhibited enhanced trained immunity, was related to the difference in sepsis 
      resistance between female and male mice. Moreover, ovariectomized (OVX) mice 
      manifested serious sepsis consequences with a weaker trained immunity effect than 
      female mice. Female bone marrow-derived macrophages (BMDMs) were also apt to be 
      polarized to the M1 phenotype in response to trained immunity in vitro. 
      Furthermore, E2 promoted trained immunity in macrophage cell lines J774 and 
      RAW264.7. E2 was also verified to facilitate trained immunity in primary BMDMs 
      from female and male mice. Mechanistically, we found that E2 inhibited the 
      nuclear translocation of RelB, which is a member of non-canonical pathway of NFkappaB 
      and contributes to macrophage polarization to change the intensity of trained 
      immunity. This study is the first to indicate the role of E2 in the trained 
      immunity induced by beta-glucan to protect against E. coli-induced sepsis via the 
      non-canonical NFkappaB pathway. These results improve our understanding of the 
      molecular mechanisms governing trained immunity in gender differences.
CI  - Copyright (c) 2020 Sun, Pan, Qu, Xu, Dou and Hou.
FAU - Sun, Zhiheng
AU  - Sun Z
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, China.
FAU - Pan, Yuchen
AU  - Pan Y
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, China.
FAU - Qu, Junxing
AU  - Qu J
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, China.
FAU - Xu, Yujun
AU  - Xu Y
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, China.
FAU - Dou, Huan
AU  - Dou H
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical 
      School, Nanjing University, Nanjing, China.
FAU - Hou, Yayi
AU  - Hou Y
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical 
      School, Nanjing University, Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200722
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 0 (Relb protein, mouse)
RN  - 0 (beta-Glucans)
RN  - 147337-75-5 (Transcription Factor RelB)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Adaptive Immunity/*drug effects
MH  - Animals
MH  - Biomarkers
MH  - Cell Line, Tumor
MH  - Cell Plasticity/immunology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Disease Resistance/drug effects/immunology
MH  - Estradiol/*pharmacology
MH  - Female
MH  - Humans
MH  - Macrophage Activation/drug effects/immunology
MH  - Macrophages/drug effects/immunology/metabolism
MH  - Male
MH  - Mice
MH  - RAW 264.7 Cells
MH  - Sepsis/drug therapy/*immunology/*metabolism/microbiology
MH  - Sex Factors
MH  - Transcription Factor RelB/*metabolism
MH  - beta-Glucans/pharmacology
PMC - PMC7387432
OTO - NOTNLM
OT  - estradiol
OT  - gender difference
OT  - macrophages
OT  - sepsis
OT  - trained immunity
EDAT- 2020/08/15 06:00
MHDA- 2021/04/21 06:00
PMCR- 2020/01/01
CRDT- 2020/08/15 06:00
PHST- 2019/11/29 00:00 [received]
PHST- 2020/06/16 00:00 [accepted]
PHST- 2020/08/15 06:00 [entrez]
PHST- 2020/08/15 06:00 [pubmed]
PHST- 2021/04/21 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.01591 [doi]
PST - epublish
SO  - Front Immunol. 2020 Jul 22;11:1591. doi: 10.3389/fimmu.2020.01591. eCollection 
      2020.