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, ) 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. 1. Introduction Alcoholic liver disease is becoming more and more widespread but the mechanisms that underlie the condition remain unknown. The typical characteristics of alcoholic liver disease are hepatic steatosis (otherwise known as fatty liver), hepatitis, fibrosis, and cirrhosis. Hospital mortality rates for alcoholic hepatitis can be as high as 60%, and mortality is often due to failure and cirrhosis of the liver [1]. Complex immune responses play an important role in the development of alcoholic liver disease [2]. Chronic long-term intake of alcohol impairs the protective mechanisms of the gut; this results in increased serum levels of lipopolysaccharide (LPS) in the area of the portal vein, which in turn activates Kupffer cells. The activated Kupffer cells secrete inflammatory cytokines, such as tumor necrosis factor α (TNF-α), which initiate a cascade of inflammatory events that can lead to inflammation. T helper 17 (TH17) cells are a newly discovered subset of T helper cells that are independent of the traditional lineages of TH1 and TH2 cells. TH17 cells appear to be involved in many autoimmune diseases [3]. Cytokine
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