Ma, KL;
Wu, Y;
Zhang, Y;
Wang, GH;
Hu, ZB;
Ruan, XZ;
(2018)
Activation of the CXCL16/CXCR6 pathway promotes lipid deposition in fatty livers of apolipoprotein E knockout mice and HepG2 cells.
American Journal of Translational Research
, 10
(6)
pp. 1802-1816.
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Abstract
Non-alcoholic fatty liver disease (NAFLD), characterised by early lipid accumulation and subsequent inflammation in the liver, is becoming a worldwide challenge due to its increasing prevalence in developing and developed countries. This study aimed to investigate the role of CXC chemokine ligand 16 (CXCL16) and its receptor CXC chemokine receptor 6 (CXCR6) in NAFLD under inflammation. We used IL-1β stimulation in human hepatoblastoma cell line (HepG2) for in vitro studies and casein injection in apolipoprotein E knockout mice in vivo to induce inflammatory stress. The effects of inflammation on cholesterol accumulation were examined by histochemical staining and a quantitative intracellular cholesterol assay. The gene and protein expression of molecules involved in CXCL16/CXCR6 pathway and extracellular matrix (ECM) were examined by real-time polymerase chain reaction (PCR) and Western blotting. The fluorescence intensity of reactive oxygen species (ROS) was assessed by flow cytometry. Results showed that significantly elevated levels of serum amyloid protein A in casein-injected mice confirmed the successful induction of inflamed NAFLD model. Inflammation significantly increased lipid accumulation in livers compared with the high-fat diet group and the controls. Furthermore, inflammation increased the expression of CXCL16, CXCR6, and adisintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in livers, accompanied with increased ECM expression and ROS production. These effects were further confirmed by in vitro studies. Interestingly, CXCL16 gene knockdown in HepG2 cells induced by CXCL16 siRNA resulted in decreased lipid accumulation, ECM excretion, and ROS production. These findings demonstrated that inflammation-mediated activation of CXCL16/CXCR6 is involved in the progression of NAFLD.
| Type: | Article |
|---|---|
| Title: | Activation of the CXCL16/CXCR6 pathway promotes lipid deposition in fatty livers of apolipoprotein E knockout mice and HepG2 cells |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | http://www.ajtr.org/V10_No6.html |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution-NonCommercial 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 https://creativecommons.org/licenses/by-nc/4.0/deed.en |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, Medicine, Research & Experimental, Research & Experimental Medicine, Non-alcoholic fatty liver disease, inflammatory stress, CXCL16/CXCR6 pathway, CXC CHEMOKINE LIGAND-16, LOW-DENSITY-LIPOPROTEIN, SCAVENGER RECEPTOR, DISEASE, ADAM10, CHOLESTEROL, DISINTEGRIN, EXPRESSION, FIBROSIS, ADHESION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10080138 |
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