期刊
MEDICINA-LITHUANIA
卷 58, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/medicina58060761
关键词
chemokine; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; inflammation; immune cells
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, and hepatic inflammation plays a crucial role in its development. Chemokines, especially CCL2 and CCL5, are important in inducing insulin resistance, steatosis, inflammation, and fibrosis in NAFLD. Cenicriviroc (CVC), a dual antagonist of chemokine receptors, has shown potential as a therapeutic approach for NASH-associated liver fibrosis.
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.
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