Anti-IL-17 antibody improves hepatic steatosis by suppressing interleukin-17-related fatty acid synthesis and metabolism

Clin Dev Immunol. 2013:2013:253046. doi: 10.1155/2013/253046. Epub 2013 Dec 17.

Abstract

To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD) at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD. A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups. The proteomic analysis was performed by two-dimensional difference gel electrophoresis. Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS) for protein identification. Additionally, expression levels of selected proteins were confirmed by western blot. Transcriptional levels of some selected proteins were determined by RT-PCR. Expression levels of 95 protein spots changed significantly (ratio >1.5, P < 0.05) during the development of ALD. Sterol regulatory element-binding protein-lc (SREBP-1c), carbohydrate response element binding protein (ChREBP), enoyl-coenzyme A hydratase (ECHS1), and peroxisome proliferator-activated receptor alpha (PPAR-α) were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α. The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology*
  • Cell Line
  • Fatty Acids / metabolism*
  • Fatty Liver / genetics
  • Fatty Liver / immunology
  • Fatty Liver / metabolism*
  • Gene Expression Profiling
  • Humans
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / metabolism*
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Proteomics / methods

Substances

  • Antibodies, Monoclonal
  • Fatty Acids
  • Interleukin-17