PMID- 30842741
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 10
DP  - 2019
TI  - IL-1beta and TNFalpha Differentially Influence NF-kappaB Activity and FasL-Induced Apoptosis 
      in Primary Murine Hepatocytes During LPS-Induced Inflammation.
PG  - 117
LID - 10.3389/fphys.2019.00117 [doi]
LID - 117
AB  - Macrophage-derived cytokines largely influence the behavior of hepatocytes during 
      an inflammatory response. We previously reported that both TNFalpha and IL-1beta, which 
      are released by macrophages upon LPS stimulation, affect Fas ligand 
      (FasL)-induced apoptotic signaling. Whereas TNFalpha preincubation leads to elevated 
      levels of caspase-3 activity and cell death, pretreatment with IL-1beta induces 
      increased caspase-3 activity but keeps cells alive. We now report that IL-1beta and 
      TNFalpha differentially influence NF-kappaB activity resulting in a differential 
      upregulation of target genes, which may contribute to the distinct effects on 
      cell viability. A reduced NF-kappaB activation model was established to further 
      investigate the molecular mechanisms which determine the distinct cell fate 
      decisions after IL-1beta and TNFalpha stimulation. To study this aspect in a more 
      physiological setting, we used supernatants from LPS-stimulated bone 
      marrow-derived macrophages (BMDMs). The treatment of hepatocytes with the BMDM 
      supernatant, which contains both IL-1beta and TNFalpha, sensitized to FasL-induced 
      caspase-3 activation and cell death. However, when TNFalpha action was blocked by 
      neutralizing antibodies, cell viability after stimulation with the BMDM 
      supernatant and FasL increased as compared to single FasL stimulation. This 
      indicates the important role of TNFalpha in the sensitization of apoptosis in 
      hepatocytes. These results give first insights into the complex interplay between 
      macrophages and hepatocytes which may influence life/death decisions of 
      hepatocytes during an inflammatory reaction of the liver in response to a 
      bacterial infection.
FAU - Rex, Julia
AU  - Rex J
AD  - Institute for System Dynamics, University of Stuttgart, Stuttgart, Germany.
FAU - Lutz, Anna
AU  - Lutz A
AD  - Department of Pharmaceutical Biology and Biotechnology, Albert Ludwigs University 
      Freiburg, Freiburg, Germany.
FAU - Faletti, Laura E
AU  - Faletti LE
AD  - Institute of Molecular Medicine and Cell Research, Albert Ludwigs University 
      Freiburg, Freiburg, Germany.
FAU - Albrecht, Ute
AU  - Albrecht U
AD  - Clinic of Gastroenterology, Hepatology and Infection Diseases, 
      Heinrich-Heine-University, Duesseldorf, Germany.
FAU - Thomas, Maria
AU  - Thomas M
AD  - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and 
      University of Tuebingen, Tuebingen, Germany.
FAU - Bode, Johannes G
AU  - Bode JG
AD  - Clinic of Gastroenterology, Hepatology and Infection Diseases, 
      Heinrich-Heine-University, Duesseldorf, Germany.
FAU - Borner, Christoph
AU  - Borner C
AD  - Department of Pharmaceutical Biology and Biotechnology, Albert Ludwigs University 
      Freiburg, Freiburg, Germany.
AD  - Spemann Graduate School of Biology and Medicine, Albert Ludwigs University 
      Freiburg, Freiburg, Germany.
AD  - BIOSS Centre for Biological Signaling Studies, Albert Ludwigs University 
      Freiburg, Freiburg, Germany.
FAU - Sawodny, Oliver
AU  - Sawodny O
AD  - Institute for System Dynamics, University of Stuttgart, Stuttgart, Germany.
FAU - Merfort, Irmgard
AU  - Merfort I
AD  - Department of Pharmaceutical Biology and Biotechnology, Albert Ludwigs University 
      Freiburg, Freiburg, Germany.
AD  - Spemann Graduate School of Biology and Medicine, Albert Ludwigs University 
      Freiburg, Freiburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20190220
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6391654
OTO - NOTNLM
OT  - LPS-induced inflammation
OT  - apoptosis
OT  - macrophages
OT  - primary murine hepatocytes
OT  - signaling
EDAT- 2019/03/08 06:00
MHDA- 2019/03/08 06:01
PMCR- 2019/02/20
CRDT- 2019/03/08 06:00
PHST- 2017/12/29 00:00 [received]
PHST- 2019/01/30 00:00 [accepted]
PHST- 2019/03/08 06:00 [entrez]
PHST- 2019/03/08 06:00 [pubmed]
PHST- 2019/03/08 06:01 [medline]
PHST- 2019/02/20 00:00 [pmc-release]
AID - 10.3389/fphys.2019.00117 [doi]
PST - epublish
SO  - Front Physiol. 2019 Feb 20;10:117. doi: 10.3389/fphys.2019.00117. eCollection 
      2019.