Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu

Abstract

AbstractPhysical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis. Voluntary distance running increased to an average of 10.3 km/day after a learning curve. Running lead to a decrease in the absolute numbers of intrahepatic CD4+ T and B lymphocytes and macrophages after 7 weeks. In parallel, hepatic mRNA expression of inflammatory cytokines including IL-6 and IL-1beta, TGF-beta and monocyte chemoattractant protein-1 (MCP-1/CCL2) were suppressed, while TNF-α was not affected by exercise. Likewise, expression of the macrophage-specific antigen F4/80 was downregulated 1.6-fold from exercise. Notably, acute liver injury from GaIN/LPS was significantly blunted following 7 weeks of voluntary exercise as determined by liver histology, a 84.6% reduction of alanine aminotransferase (P<0.01) and a 54.6% reduction of aspartate aminotransferase (P<0.05) compared with sedentary mice. Additionally, proinflammatory cytokines, activation of caspase 3 and JNK were significantly lower, while antiapoptotic protein A20 increased. Voluntary distance running alters the intrahepatic immune phenotype producing an environment that is less susceptible to acute liver injury.

Autoren

Yvonne Huber
Nadine Gehrke
Jana Biedenbach
Susanne Helmig
Perikles Simon
Beate K Straub
Ina Bergheim
Tobias Huber
Detlef Schuppan
Peter R Galle
Marcus A Wörns
Marcus Schuchmann
Jörn M Schattenberg

DOI

10.1038/cddis.2017.266

eISSN

2041-4889

Ausgabe der Veröffentlichung

6

Zeitschrift

Cell Death & Disease

Sprache

en

Online publication date

2017

Paginierung

e2893 - e2893

Status

Published online

Herausgeber

Springer Science and Business Media LLC

Herausgeber URL

http://dx.doi.org/10.1038/cddis.2017.266

Datum der Datenerfassung

2022

Titel

Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu

Ausgabe der Zeitschrift

8

Datenquelle: Crossref

Abstract

Physical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis. Voluntary distance running increased to an average of 10.3 km/day after a learning curve. Running lead to a decrease in the absolute numbers of intrahepatic CD4+ T and B lymphocytes and macrophages after 7 weeks. In parallel, hepatic mRNA expression of inflammatory cytokines including IL-6 and IL-1beta, TGF-beta and monocyte chemoattractant protein-1 (MCP-1/CCL2) were suppressed, while TNF-α was not affected by exercise. Likewise, expression of the macrophage-specific antigen F4/80 was downregulated 1.6-fold from exercise. Notably, acute liver injury from GaIN/LPS was significantly blunted following 7 weeks of voluntary exercise as determined by liver histology, a 84.6% reduction of alanine aminotransferase (P<0.01) and a 54.6% reduction of aspartate aminotransferase (P<0.05) compared with sedentary mice. Additionally, proinflammatory cytokines, activation of caspase 3 and JNK were significantly lower, while antiapoptotic protein A20 increased. Voluntary distance running alters the intrahepatic immune phenotype producing an environment that is less susceptible to acute liver injury.

Addresses

I. Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Autoren

Yvonne Huber
Nadine Gehrke
Jana Biedenbach
Susanne Helmig
Perikles Simon
Beate K Straub
Ina Bergheim
Tobias Huber
Detlef Schuppan
Peter R Galle
Marcus A Wörns
Marcus Schuchmann
Jörn M Schattenberg

DOI

10.1038/cddis.2017.266

eISSN

2041-4889

Externe Identifier

PubMed Identifier: 28640248
PubMed Central ID: PMC5520921

Open access

true

ISSN

2041-4889

Ausgabe der Veröffentlichung

6

Zeitschrift

Cell death & disease

Schlüsselwörter

Liver
Animals
Mice, Inbred C57BL
Liver Failure, Acute
Inflammation
Body Weight
JNK Mitogen-Activated Protein Kinases
Galactosamine
Lipopolysaccharides
Tumor Necrosis Factor-alpha
NF-kappa B
Inflammation Mediators
Chemokines
Cytokines
Liver Function Tests
Models, Animal
Physical Conditioning, Animal
Chemotaxis
Enzyme Activation
Male
Receptors, Pattern Recognition
Alarmins

Sprache

eng

Medium

Electronic

Online publication date

2017

Open access status

Open Access

Paginierung

e2893

Datum der Veröffentlichung

2017

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2017

Titel

Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

8

Files

https://www.nature.com/articles/cddis2017266.pdf https://europepmc.org/articles/PMC5520921?pdf=render

Datenquelle: Europe PubMed Central

Abstract

Physical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis. Voluntary distance running increased to an average of 10.3 km/day after a learning curve. Running lead to a decrease in the absolute numbers of intrahepatic CD4+ T and B lymphocytes and macrophages after 7 weeks. In parallel, hepatic mRNA expression of inflammatory cytokines including IL-6 and IL-1beta, TGF-beta and monocyte chemoattractant protein-1 (MCP-1/CCL2) were suppressed, while TNF-α was not affected by exercise. Likewise, expression of the macrophage-specific antigen F4/80 was downregulated 1.6-fold from exercise. Notably, acute liver injury from GaIN/LPS was significantly blunted following 7 weeks of voluntary exercise as determined by liver histology, a 84.6% reduction of alanine aminotransferase (P<0.01) and a 54.6% reduction of aspartate aminotransferase (P<0.05) compared with sedentary mice. Additionally, proinflammatory cytokines, activation of caspase 3 and JNK were significantly lower, while antiapoptotic protein A20 increased. Voluntary distance running alters the intrahepatic immune phenotype producing an environment that is less susceptible to acute liver injury.

Date of acceptance

2017

Autoren

Yvonne Huber
Nadine Gehrke
Jana Biedenbach
Susanne Helmig
Perikles Simon
Beate K Straub
Ina Bergheim
Tobias Huber
Detlef Schuppan
Peter R Galle
Marcus A Wörns
Marcus Schuchmann
Jörn M Schattenberg

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/28640248

DOI

10.1038/cddis.2017.266

eISSN

2041-4889

Externe Identifier

PubMed Central ID: PMC5520921

Ausgabe der Veröffentlichung

6

Zeitschrift

Cell Death Dis

Schlüsselwörter

Alarmins
Animals
Body Weight
Chemokines
Chemotaxis
Cytokines
Enzyme Activation
Galactosamine
Inflammation
Inflammation Mediators
JNK Mitogen-Activated Protein Kinases
Lipopolysaccharides
Liver
Liver Failure, Acute
Liver Function Tests
Male
Mice, Inbred C57BL
Models, Animal
NF-kappa B
Physical Conditioning, Animal
Receptors, Pattern Recognition
Tumor Necrosis Factor-alpha

Sprache

eng

Country

England

Paginierung

e2893

PII

cddis2017266

Datum der Veröffentlichung

2017

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2018

Titel

Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

8

Datenquelle: PubMed

Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu

Files

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