PMID- 28720906
OWN - NLM
STAT- MEDLINE
DCOM- 20190605
LR  - 20190605
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jul 18
TI  - Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in 
      human adipocytes.
PG  - 5691
LID - 10.1038/s41598-017-05932-7 [doi]
LID - 5691
AB  - High serum concentrations of TNF-related apoptosis-inducing ligand (TRAIL), a 
      member of the tumor necrosis factor protein family, are found in patients with 
      increased BMI and serum lipid levels. In a model of murine obesity, both the 
      expression of TRAIL and its receptor (TRAIL-R) is elevated in adipose tissue. 
      Accordingly, TRAIL has been proposed as an important mediator of adipose tissue 
      inflammation and obesity-associated diseases. The aim of this study was to 
      investigate if TRAIL regulates inflammatory processes at the level of the 
      adipocyte. Using human Simpson-Golabi-Behmel syndrome (SGBS) cells as a model 
      system, we found that TRAIL induces an inflammatory response in both 
      preadipocytes and adipocytes. It stimulates the expression of interleukin 6 
      (IL-6), interleukin 8 (IL-8) as well as the chemokines monocyte chemoattractant 
      protein-1 (MCP-1) and chemokine C-C motif ligand 20 (CCL-20) in a time- and 
      dose-dependent manner. By using small molecule inhibitors, we found that both the 
      NFkappaB and the ERK1/2 pathway are crucial for mediating the effect of TRAIL. Taken 
      together, we identified a novel pro-inflammatory function of TRAIL in human 
      adipocytes. Our findings suggest that targeting the TRAIL/TRAIL-R system might be 
      a useful strategy to tackle obesity-associated adipose tissue inflammation.
FAU - Zoller, Verena
AU  - Zoller V
AD  - Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and 
      Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
FAU - Funcke, Jan-Bernd
AU  - Funcke JB
AD  - Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and 
      Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
FAU - Roos, Julian
AU  - Roos J
AD  - Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and 
      Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
FAU - Dahlhaus, Meike
AU  - Dahlhaus M
AD  - Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and 
      Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
FAU - Abd El Hay, Muad
AU  - Abd El Hay M
AUID- ORCID: 0000-0002-5082-1216
AD  - Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and 
      Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
FAU - Holzmann, Karlheinz
AU  - Holzmann K
AD  - Core Facility Genomics, Ulm University, Ulm, Germany.
FAU - Marienfeld, Ralf
AU  - Marienfeld R
AD  - Institute of Pathology, Ulm University, Ulm, Germany; Department of Pediatric and 
      Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
FAU - Kietzmann, Thomas
AU  - Kietzmann T
AUID- ORCID: 0000-0003-0242-8636
AD  - Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of 
      Oulu, Oulu, Finland.
FAU - Debatin, Klaus-Michael
AU  - Debatin KM
AD  - Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, 
      Ulm, Germany.
FAU - Wabitsch, Martin
AU  - Wabitsch M
AD  - Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and 
      Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
FAU - Fischer-Posovszky, Pamela
AU  - Fischer-Posovszky P
AD  - Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and 
      Adolescent Medicine, University Medical Center Ulm, Ulm, Germany. 
      pamela.fischer@uniklinik-ulm.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170718
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL20)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - Simpson-Golabi-Behmel syndrome
SB  - IM
MH  - Adipocytes/*drug effects
MH  - Adult
MH  - Arrhythmias, Cardiac
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CCL20
MH  - Genetic Diseases, X-Linked
MH  - Gigantism
MH  - Heart Defects, Congenital
MH  - Humans
MH  - Inflammation/*physiopathology
MH  - Intellectual Disability
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Signal Transduction
MH  - TNF-Related Apoptosis-Inducing Ligand/*pharmacology
PMC - PMC5515939
COIS- The authors declare that they have no competing interests.
EDAT- 2017/07/20 06:00
MHDA- 2019/06/06 06:00
PMCR- 2017/07/18
CRDT- 2017/07/20 06:00
PHST- 2017/02/08 00:00 [received]
PHST- 2017/06/06 00:00 [accepted]
PHST- 2017/07/20 06:00 [entrez]
PHST- 2017/07/20 06:00 [pubmed]
PHST- 2019/06/06 06:00 [medline]
PHST- 2017/07/18 00:00 [pmc-release]
AID - 10.1038/s41598-017-05932-7 [pii]
AID - 5932 [pii]
AID - 10.1038/s41598-017-05932-7 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jul 18;7(1):5691. doi: 10.1038/s41598-017-05932-7.