Steatosis induced CCL5 contributes to early-stage liver fibrosis in nonalcoholic fatty liver disease progress

Li, Binghang; He, Fangping; Yang, Xin; Chen, Yuanwen; Fan, Jian‐Gao

doi:10.1016/j.trsl.2016.08.006

Cited by 47 publications

(32 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have reported higher levels of circulating CCL5 in patients with NAFLD . CCL5 overexpression in the liver of mouse models of NAFLD mediates the migration of gut‐derived lymphocytes from mesenteric lymph nodes, resulting in liver injury and hepatic CD4 + T and CD8 + T‐cell activation .…”

Section: Discussionmentioning

confidence: 75%

Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 75%

Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease

et al. 2018

View full text Add to dashboard Cite

show abstract

“…IL-34 has recently been identified as a significant predictor of cardiovascular mortality, and is proposed to contribute to atherosclerosis progression by promoting the release of other proinflammatory cytokines including IL-1β, IL-6 and TNF-α [26]. Similarly, CCL5 and CCL20, both potent chemokines, are increased in serum from individuals with NAFLD/NASH, and originate from both hepatocytes and activated HSC [27,28]. Most recently, circulating IL-6 was independently associated with subclinical atherosclerosis in an NAFLD subgroup of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort [29 ▪▪ ].…”

Section: Hepatic Stellate Cellsmentioning

confidence: 99%

Non-parenchymal hepatic cell lipotoxicity and the coordinated progression of non-alcoholic fatty liver disease and atherosclerosis

Peters¹,

Wilson²,

Borradaile³

2018

Current Opinion in Lipidology

View full text Add to dashboard Cite

Purpose of reviewNon-alcoholic fatty liver disease (NAFLD) appears to be independently associated with the development of atherosclerosis. The biological mechanisms underlying this association are complex, and likely involve liver-resident cell types other than hepatocytes. Thus, we review recent evidence that non-parenchymal hepatic cell responses to lipid excess contribute to the pathogenesis of both NAFLD and atherosclerosis.Recent findingsSignificant independent associations between NAFLD and atherosclerosis have been identified through cross-sectional studies and meta-analyses. Mechanistic studies in cell cultures and in rodent models suggest that liver-resident macrophages, activated hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) mount lipotoxic responses under NAFLD conditions which can contribute to the progression of both NAFLD and atherosclerosis.SummaryNon-parenchymal hepatic cell types exhibit some similarity in their responses to lipid excess, and in their pathogenic mechanisms, which likely contribute to the coordinated progression of NAFLD and atherosclerosis. In response to lipotoxic conditions, macrophages, Kupffer cells and HSC initiate robust inflammatory responses, whereas LSEC generate excess reactive oxygen species (ROS). The extent to which inflammatory cytokines and ROS produced by non-parenchymal cells contribute to the progression of both NAFLD and atherosclerosis warrants further investigation.

show abstract

“…For example, Kim et al recently reported that CCR5 is expressed on hepatocytes and is involved in their ability to accumulate fat and promote steatosis and that CCL5 is secreted by hepatocytes during steatosis. [43][44][45] Our data suggest that there might be a direct effect of CCL24 on hepatocytes, although an indirect effect could not be completely ruled out. This effect, either direct or indirect, is novel and highly interesting and needs to be further elucidated in upcoming research on CCL24.…”

Section: Discussionmentioning

confidence: 63%

A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage

Segal-Salto¹,

Barashi²,

Katav³

et al. 2020

JHEP Reports

View full text Add to dashboard Cite

Correspondence adimor@chemomab.com (A. Mor). Graphical abstract CCL24 CCR3 Immune cells C M -1 0 1 C M -1 0 1Highlights CCL24 is a chemokine that regulates inflammatory and fibrotic activities through its receptor, CCR3.Significant expression of CCL24 and CCR3 were found in liver biopsies and blood samples from patients with NAFLD/NASH. CM-101, a monoclonal antibody that selectively targets CCL24, significantly attenuates fibrotic and inflammatory processes.Blocking CCL24 may have a potential therapeutic effect in NASH and liver fibrosis. Lay summaryCCL24 is a chemokine that regulates inflammation and fibrosis. It was found to be significantly expressed in patients with non-alcoholic steatohepatitis, in whom it regulates profibrotic processes in the liver. Herein, we show that blockade of CCL24 using a monoclonal antibody robustly attenuated liver fibrosis and inflammation in animal models, thus suggesting a potential therapeutic role for an anti-CCL24 agent.Background & Aims: C-C motif chemokine ligand 24 (CCL24) is a chemokine that regulates inflammatory and fibrotic activities through its receptor, C-C motif chemokine receptor (CCR3). The aim of the study was to evaluate the involvement of the CCL24-CCR3 axis in liver fibrosis and inflammation and to assess the potential of its blockade, by a monoclonal anti-CCL24 antibody, as a therapeutic strategy for non-alcoholic steatohepatitis (NASH) and liver fibrosis. Methods: Expression of CCL24 and CCR3 was evaluated in liver biopsies and blood samples. CCL24 involvement in NAFLD/ NASH pathogenesis was assessed in Ccl24 knockout mouse using the methionine-choline deficient (MCD) diet experimental model. Antifibrotic and anti-inflammatory effects of CM-101 were tested in the MCD and STAM mouse models and in the thioacetamide (TAA) model in rats. Liver enzymes, liver morphology, histology and collagen deposition, as well as fibrosisand inflammation-related protein expression were assessed. Activation of hepatic stellate cells (HSCs) was evaluated in the human LX2 cell line.Results: Patients with NASH and advanced NAFLD exhibited significant expression of both CCL24 and CCR3 in liver and blood samples. In the experimental MCD-diet model, Ccl24 knockout mice showed an attenuated liver damage response compared to wild-type mice, exhibiting reduced histological NAFLD activity scores and fibrosis, as well as lower levels of liver enzymes. Blocking CCL24 using CM-101 robustly reduced liver damage in 3 experimental animal models (MCD, STAM and TAA), as demonstrated by attenuation of liver fibrosis and NAFLD activity score. Furthermore, blocking CCL24 by CM-101 significantly inhibited CCL24-induced HSC motility, a-SMA expression and pro-collagen I secretion.Conclusion: Our results reveal that blocking CCL24 significantly attenuates liver fibrosis and inflammation and may have a potential therapeutic effect in patients with NASH and/or liver fibrosis.

show abstract

Steatosis induced CCL5 contributes to early-stage liver fibrosis in nonalcoholic fatty liver disease progress

Cited by 47 publications

References 58 publications

Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease

Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease

Non-parenchymal hepatic cell lipotoxicity and the coordinated progression of non-alcoholic fatty liver disease and atherosclerosis

A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage

Contact Info

Product

Resources

About