Zoller, V., Funcke, J., Roos, J., Dahlhaus, M., Abd El Hay, M., Holzmann, K., Marienfeld, R., Kietzmann, T., Debatin, K., Wabitsch, M., Fischer-Posovszky, P. (2017) Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes. Scientific Reports, 7 (1), doi:10.1038/s41598-017-05932-7
Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes
|Author:||Zoller, Verena1; Funcke, Jan-Bernd1; Roos, Julian1;|
1Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center Ulm
2Core Facility Genomics, Ulm University
3Institute of Pathology, Ulm University, Ulm, Germany; Department of Pediatric and Adolescent Medicine, University Medical Center Ulm
4Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu
5Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm
6Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center Ulm
|Online Access:||PDF Full Text (PDF, 2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201709118562
|Publish Date:|| 2017-09-11
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This study was supported by the International Graduate School in Molecular Medicine at the University of Ulm (GSC270). V.Z. and J.B.F. were funded by GSC270. T.K. was supported by grants from the Academy of Finland, Biocenter Oulu and Jane and Aatos Erkko Foundation.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.