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Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation

OBJECTIVES: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has...

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Autores principales: Otterdal, Kari, Haukeland, John Willy, Yndestad, Arne, Dahl, Tuva B, Holm, Sverre, Segers, Filip M, Gladhaug, Ivar P, Konopski, Zbigniew, Damås, Jan Kristian, Halvorsen, Bente, Aukrust, Pål
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816254/
https://www.ncbi.nlm.nih.gov/pubmed/26133108
http://dx.doi.org/10.1038/ctg.2015.23
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author Otterdal, Kari
Haukeland, John Willy
Yndestad, Arne
Dahl, Tuva B
Holm, Sverre
Segers, Filip M
Gladhaug, Ivar P
Konopski, Zbigniew
Damås, Jan Kristian
Halvorsen, Bente
Aukrust, Pål
author_facet Otterdal, Kari
Haukeland, John Willy
Yndestad, Arne
Dahl, Tuva B
Holm, Sverre
Segers, Filip M
Gladhaug, Ivar P
Konopski, Zbigniew
Damås, Jan Kristian
Halvorsen, Bente
Aukrust, Pål
author_sort Otterdal, Kari
collection PubMed
description OBJECTIVES: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD). METHODS: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. RESULTS: (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H(2)O(2) (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes. CONCLUSION: We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression.
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spelling pubmed-48162542016-04-13 Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation Otterdal, Kari Haukeland, John Willy Yndestad, Arne Dahl, Tuva B Holm, Sverre Segers, Filip M Gladhaug, Ivar P Konopski, Zbigniew Damås, Jan Kristian Halvorsen, Bente Aukrust, Pål Clin Transl Gastroenterol Original Contributions OBJECTIVES: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD). METHODS: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. RESULTS: (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H(2)O(2) (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes. CONCLUSION: We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression. Nature Publishing Group 2015-07 2015-07-02 /pmc/articles/PMC4816254/ /pubmed/26133108 http://dx.doi.org/10.1038/ctg.2015.23 Text en Copyright © 2015 American College of Gastroenterology http://creativecommons.org/licenses/by-nc-nd/4.0/ Clinical and Translational Gastroenterology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Contributions
Otterdal, Kari
Haukeland, John Willy
Yndestad, Arne
Dahl, Tuva B
Holm, Sverre
Segers, Filip M
Gladhaug, Ivar P
Konopski, Zbigniew
Damås, Jan Kristian
Halvorsen, Bente
Aukrust, Pål
Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation
title Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation
title_full Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation
title_fullStr Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation
title_full_unstemmed Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation
title_short Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation
title_sort increased serum levels of light/tnfsf14 in nonalcoholic fatty liver disease: possible role in hepatic inflammation
topic Original Contributions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816254/
https://www.ncbi.nlm.nih.gov/pubmed/26133108
http://dx.doi.org/10.1038/ctg.2015.23
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