PMID- 32670276
OWN - NLM
STAT- MEDLINE
DCOM- 20210405
LR  - 20210405
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - The Receptor for Advanced Glycation Endproducts (RAGE) Contributes to Severe 
      Inflammatory Liver Injury in Mice.
PG  - 1157
LID - 10.3389/fimmu.2020.01157 [doi]
LID - 1157
AB  - Background: The receptor for advanced glycation end products (RAGE) is a 
      multiligand receptor involved in a number of processes and disorders. While it is 
      known that RAGE-signaling can contribute to toxic liver damage and fibrosis, its 
      role in acute inflammatory liver injury and septic multiorgan failure is yet 
      undefined. We examined RAGE in lipopolysaccharide (LPS) induced acute liver 
      injury of D-galN sensitized mice as a classical model for tumor necrosis factor 
      alpha (TNF-alpha) dependent inflammatory organ damage. Methods: Mice (Rage-/- and 
      C57BL/6) were intraperitoneally injected with D-galN (300 mg/kg) and LPS (10 
      mug/kg). Animals were monitored clinically, and cytokines, damage associated 
      molecular pattern molecules (DAMPs) as well as liver enzymes were determined in 
      serum. Liver histology, hepatic cytokines as well as RAGE mRNA expression were 
      analyzed. Cellular activation and functionality were evaluated by flow cytometry 
      both in bone marrow- and liver-derived cells. Results: Genetic deficiency of RAGE 
      significantly reduced the mortality of mice exposed to LPS/D-galN. Hepatocyte 
      damage markers were reduced in Rage-/- mice, and liver histopathology was less 
      severe. Rage-/- mice produced less pro-inflammatory cytokines and DAMPs in serum 
      and liver. While immune cell functions appeared normal, TNF-alpha production by 
      hepatocytes was reduced in Rage-/- mice. Conclusions: We found that RAGE deletion 
      attenuated the expression of pro-inflammatory cytokines and DAMPs in hepatocytes 
      without affecting cellular immune functions in the LPS/D-galN model of murine 
      liver injury. Our data highlight the importance of tissue-specific RAGE-signaling 
      also in acute inflammatory liver stress contributing to sepsis and multiorgan 
      failure.
CI  - Copyright (c) 2020 Weinhage, Wirth, Schutz, Becker, Lueken, Skryabin, Wittkowski 
      and Foell.
FAU - Weinhage, Toni
AU  - Weinhage T
AD  - Department of Pediatric Rheumatology and Immunology, University of Munster, 
      Munster, Germany.
FAU - Wirth, Timo
AU  - Wirth T
AD  - Department of Neurology With Institute of Translational Neurology, University 
      Hospital Munster, Munster, Germany.
FAU - Schutz, Paula
AU  - Schutz P
AD  - Department of Pediatric Rheumatology and Immunology, University of Munster, 
      Munster, Germany.
FAU - Becker, Philipp
AU  - Becker P
AD  - Department of Pediatric Rheumatology and Immunology, University of Munster, 
      Munster, Germany.
FAU - Lueken, Aloys
AU  - Lueken A
AD  - Department of Pediatric Rheumatology and Immunology, University of Munster, 
      Munster, Germany.
FAU - Skryabin, Boris V
AU  - Skryabin BV
AD  - Core Facility of Transgenic Animal and Genetic Engineering Models (TRAM), 
      University of Munster, Munster, Germany.
FAU - Wittkowski, Helmut
AU  - Wittkowski H
AD  - Department of Pediatric Rheumatology and Immunology, University of Munster, 
      Munster, Germany.
FAU - Foell, Dirk
AU  - Foell D
AD  - Department of Pediatric Rheumatology and Immunology, University of Munster, 
      Munster, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200603
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Ager protein, mouse)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptor for Advanced Glycation End Products)
SB  - IM
MH  - Animals
MH  - Inflammation/chemically induced/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Liver Failure, Acute/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptor for Advanced Glycation End Products/*metabolism
MH  - Sepsis/complications/metabolism/pathology
PMC - PMC7326105
OTO - NOTNLM
OT  - DAMPs
OT  - PAMPs
OT  - RAGE
OT  - inflammatory liver injury
OT  - sepsis
EDAT- 2020/07/17 06:00
MHDA- 2021/04/07 06:00
PMCR- 2020/01/01
CRDT- 2020/07/17 06:00
PHST- 2020/02/12 00:00 [received]
PHST- 2020/05/11 00:00 [accepted]
PHST- 2020/07/17 06:00 [entrez]
PHST- 2020/07/17 06:00 [pubmed]
PHST- 2021/04/07 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.01157 [doi]
PST - epublish
SO  - Front Immunol. 2020 Jun 3;11:1157. doi: 10.3389/fimmu.2020.01157. eCollection 
      2020.