title: Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation.
abstract: OBJECTIVE
  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) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway [2] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.affiliation: Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: John Willy
authors.initials: JW
authors.lastname: Haukeland
authors.affiliation: 1] Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway [2] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway [3] K.G. Jebsen Inflammatory Research Center, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.affiliation: 1] Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway [2] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tuva B
authors.initials: TB
authors.lastname: Dahl
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Holm
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Filip M
authors.initials: FM
authors.lastname: Segers
authors.affiliation: 1] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway [2] Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Ivar P
authors.initials: IP
authors.lastname: Gladhaug
authors.affiliation: Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Konopski
authors.affiliation: 1] Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, St Olavs Hospital, Trondheim, Norway [2] Department of Infectious Diseases, St Olavs Hospital, Trondheim, Norway.
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.affiliation: 1] Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway [2] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway [3] K.G. Jebsen Inflammatory Research Center, Oslo, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.affiliation: 1] Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway [2] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway [3] K.G. Jebsen Inflammatory Research Center, Oslo, Norway [4] Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust