Small heterodimer partner deficiency exacerbates binge drinking‑induced liver injury via modulation of natural killer T cell and neutrophil infiltration

Go,Min‑Jeong; Noh,Jung‑Ran; Hwang,Jung Hwan; Kim,Kyoung‑Shim; Choi,Dong‑Hee; Lee,Jong‑Soo; Kim,Yong‑Hoon; Lee,Chul‑Ho

doi:10.3892/mmr.2018.8505

Small heterodimer partner deficiency exacerbates binge drinking‑induced liver injury via modulation of natural killer T cell and neutrophil infiltration

Authors:
- Min‑Jeong Go
- Jung‑Ran Noh
- Jung Hwan Hwang
- Kyoung‑Shim Kim
- Dong‑Hee Choi
- Jong‑Soo Lee
- Yong‑Hoon Kim
- Chul‑Ho Lee
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Affiliations: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea, Department of Veterinary Microbiology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea
Published online on: January 26, 2018 https://doi.org/10.3892/mmr.2018.8505
Pages: 4989-4998
Copyright: © Go et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Binge drinking among alcohol consumers is a common occurrence, and may result in the development of numerous diseases, including liver disorders. It has previously been reported that natural killer T (NKT) cells induce alcohol‑associated liver injury by promoting neutrophil infiltration. In the present study, the role of the orphan nuclear receptor small heterodimer partner (SHP), which is encoded by the NR0B2 gene, in acute binge drinking‑induced liver injury was investigated. SHP‑knockout (KO) and wild‑type (WT) control mice were intragastrically administered single doses of alcohol. The plasma concentrations of alanine aminotransferase and aspartate aminotransferase in SHP‑KO mice following alcohol treatment were significantly increased compared with WT mice. However, results of oil red O staining and 2',7'‑dichlorodihydrofluorescein diacetate staining indicated that levels of acute binge drinking‑associated hepatic lipid accumulation and oxidative stress were not significantly different between WT and SHP‑KO alcohol‑treated mice. Notably, tumor necrosis factor‑α mRNA expression in the liver of SHP‑KO mice was significantly increased following alcohol administration, compared with WT mice. Furthermore, the mRNA expression levels of C‑C motif chemokine ligand 2, C‑X‑C motif chemokine ligand 2 and interleukin‑4, which are all potent chemoattractants of NKT cells, as well as neutrophil expression levels, were significantly increased in the livers of SHP‑KO mice compared with WT mice following alcohol administration, as determined by reverse transcription‑quantitative polymerase chain reaction and flow cytometry. Enhanced infiltration of NKT cells, determined by flow cytometry, was also demonstrated in the livers of SHP‑KO mice following alcohol administration, compared with WT mice. The results of the present study indicate that SHP may be involved in liver‑associated protective mechanisms, with regards to the attenuation of damage caused by acute binge drinking, via regulation of NKT cell and neutrophil migration to the liver. The modulation of SHP may be a novel therapeutic strategy for the treatment of acute binge drinking‑induced liver injury.

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