Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes
Abstract 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 elevate...
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2017-07-01
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doaj-b533c20e2c264adf9a50186b0fc78b9b2020-12-07T23:58:40ZengNature Publishing GroupScientific Reports2045-23222017-07-017111210.1038/s41598-017-05932-7Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytesVerena Zoller0Jan-Bernd Funcke1Julian Roos2Meike Dahlhaus3Muad Abd El Hay4Karlheinz Holzmann5Ralf Marienfeld6Thomas Kietzmann7Klaus-Michael Debatin8Martin Wabitsch9Pamela Fischer-Posovszky10Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center UlmDivision of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center UlmDivision of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center UlmDivision of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center UlmDivision of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center UlmCore Facility Genomics, Ulm UniversityInstitute of Pathology, Ulm University, Ulm, Germany; Department of Pediatric and Adolescent Medicine, University Medical Center UlmFaculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of OuluDepartment of Pediatrics and Adolescent Medicine, University Medical Center UlmDivision of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center UlmDivision of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center UlmAbstract 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 NFκB 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.https://doi.org/10.1038/s41598-017-05932-7 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Verena Zoller Jan-Bernd Funcke Julian Roos Meike Dahlhaus Muad Abd El Hay Karlheinz Holzmann Ralf Marienfeld Thomas Kietzmann Klaus-Michael Debatin Martin Wabitsch Pamela Fischer-Posovszky |
spellingShingle |
Verena Zoller Jan-Bernd Funcke Julian Roos Meike Dahlhaus Muad Abd El Hay Karlheinz Holzmann Ralf Marienfeld Thomas Kietzmann Klaus-Michael Debatin Martin Wabitsch Pamela Fischer-Posovszky Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes Scientific Reports |
author_facet |
Verena Zoller Jan-Bernd Funcke Julian Roos Meike Dahlhaus Muad Abd El Hay Karlheinz Holzmann Ralf Marienfeld Thomas Kietzmann Klaus-Michael Debatin Martin Wabitsch Pamela Fischer-Posovszky |
author_sort |
Verena Zoller |
title |
Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes |
title_short |
Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes |
title_full |
Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes |
title_fullStr |
Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes |
title_full_unstemmed |
Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes |
title_sort |
trail (tnf-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-07-01 |
description |
Abstract 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 NFκB 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. |
url |
https://doi.org/10.1038/s41598-017-05932-7 |
work_keys_str_mv |
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