An Update on the Chemokine System in the Development of NAFLD
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Sustained hepatic inflammation is a key driver of the transition from simple fatty liver to nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. Hepatic inflammation is orchestrated by...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/58/6/761 |
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| author | Naoto Nagata Guanliang Chen Liang Xu Hitoshi Ando |
| author_facet | Naoto Nagata Guanliang Chen Liang Xu Hitoshi Ando |
| author_sort | Naoto Nagata |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Sustained hepatic inflammation is a key driver of the transition from simple fatty liver to nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. Hepatic inflammation is orchestrated by chemokines, a family of chemoattractant cytokines that are produced by hepatocytes, Kupffer cells (liver resident macrophages), hepatic stellate cells, endothelial cells, and vascular smooth muscle cells. Over the last three decades, accumulating evidence from both clinical and experimental investigations demonstrated that chemokines and their receptors are increased in the livers of NAFLD patients and that CC chemokine ligand (CCL) 2 and CCL5 in particular play a pivotal role in inducing insulin resistance, steatosis, inflammation, and fibrosis in liver disease. Cenicriviroc (CVC), a dual antagonist of these chemokines’ receptors, CCR2 and CCR5, has been tested in clinical trials in patients with NASH-associated liver fibrosis. Additionally, recent studies revealed that other chemokines, such as CCL3, CCL25, CX3C chemokine ligand 1 (CX3CL1), CXC chemokine ligand 1 (CXCL1), and CXCL16, can also contribute to the pathogenesis of NAFLD. Here, we review recent updates on the roles of chemokines in the development of NAFLD and their blockade as a potential therapeutic approach. |
| first_indexed | 2024-03-09T23:07:20Z |
| format | Article |
| id | doaj.art-e0ba8b00e44a424e8dde686ea3903204 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-09T23:07:20Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-e0ba8b00e44a424e8dde686ea39032042023-11-23T17:52:09ZengMDPI AGMedicina1010-660X1648-91442022-06-0158676110.3390/medicina58060761An Update on the Chemokine System in the Development of NAFLDNaoto Nagata0Guanliang Chen1Liang Xu2Hitoshi Ando3Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, JapanDepartment of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanSchool of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaDepartment of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, JapanNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Sustained hepatic inflammation is a key driver of the transition from simple fatty liver to nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. Hepatic inflammation is orchestrated by chemokines, a family of chemoattractant cytokines that are produced by hepatocytes, Kupffer cells (liver resident macrophages), hepatic stellate cells, endothelial cells, and vascular smooth muscle cells. Over the last three decades, accumulating evidence from both clinical and experimental investigations demonstrated that chemokines and their receptors are increased in the livers of NAFLD patients and that CC chemokine ligand (CCL) 2 and CCL5 in particular play a pivotal role in inducing insulin resistance, steatosis, inflammation, and fibrosis in liver disease. Cenicriviroc (CVC), a dual antagonist of these chemokines’ receptors, CCR2 and CCR5, has been tested in clinical trials in patients with NASH-associated liver fibrosis. Additionally, recent studies revealed that other chemokines, such as CCL3, CCL25, CX3C chemokine ligand 1 (CX3CL1), CXC chemokine ligand 1 (CXCL1), and CXCL16, can also contribute to the pathogenesis of NAFLD. Here, we review recent updates on the roles of chemokines in the development of NAFLD and their blockade as a potential therapeutic approach.https://www.mdpi.com/1648-9144/58/6/761chemokinenonalcoholic fatty liver diseasenonalcoholic steatohepatitisinflammationimmune cells |
| spellingShingle | Naoto Nagata Guanliang Chen Liang Xu Hitoshi Ando An Update on the Chemokine System in the Development of NAFLD Medicina chemokine nonalcoholic fatty liver disease nonalcoholic steatohepatitis inflammation immune cells |
| title | An Update on the Chemokine System in the Development of NAFLD |
| title_full | An Update on the Chemokine System in the Development of NAFLD |
| title_fullStr | An Update on the Chemokine System in the Development of NAFLD |
| title_full_unstemmed | An Update on the Chemokine System in the Development of NAFLD |
| title_short | An Update on the Chemokine System in the Development of NAFLD |
| title_sort | update on the chemokine system in the development of nafld |
| topic | chemokine nonalcoholic fatty liver disease nonalcoholic steatohepatitis inflammation immune cells |
| url | https://www.mdpi.com/1648-9144/58/6/761 |
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