C C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

Zhuo, Jianyong; Lu, Di; Lin, Zuyuan; Cen, Beini; Wei, Xuyong; Xie, Haiyang; Zheng, Shusen

doi:10.1016/j.hbpd.2019.12.006

Cited by 13 publications

(7 citation statements)

References 30 publications

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Section: Ccl16 In Liver Diseasementioning

confidence: 99%

“…Recent studies have shown that CCL16 expression is downregulated in LO2 after LPS and hypoxia stimulation (31). CCL16 could reduce liver cirrhosis by inhibiting the activation of HSCs in mice, suggesting that it may be a marker to predict the occurrence and progression of liver cirrhosis (31). There was no significant difference in the expression level of CCL16 between HCC tumor tissues and HCC-adjacent tissues, and the expression level of CCL16 had no correlation with the prognosis of HCC patients based on the TCGA LIHC dataset (Figures 3G, H).…”

Section: Ccl16 In Liver Diseasementioning

confidence: 99%

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Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease

et al. 2022

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Chemokines are a family of cytokines that orchestrate the migration and positioning of immune cells within tissues and are critical for the function of the immune system. CCR2 participates in liver pathology, including acute liver injury, chronic hepatitis, fibrosis/cirrhosis, and tumor progression, by mediating the recruitment of immune cells to inflammation and tumor sites. Although a variety of chemokines have been well studied in various diseases, there is no comprehensive review presenting the roles of all known chemokine ligands of CCR2 (CCL2, CCL7, CCL8, CCL12, CCL13, CCL16, and PSMP) in liver disease, and this review aims to fill this gap. The introduction of each chemokine includes its discovery, its corresponding chemotactic receptors, physiological functions and roles in inflammation and tumors, and its impact on different immune cell subgroups.

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Section: Ccl16 In Liver Diseasementioning

confidence: 99%

Section: Ccl16 In Liver Diseasementioning

confidence: 99%

Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease

et al. 2022

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“…A protective effect of CCR5Delta32 in recovery from an HBV infection is observed ( Thio et al, 2007 ). Its ligand, CCL16 also shows an encouraging effect on inhibiting the progression of LC via inactivating HSCs ( Zhuo et al, 2020 ). In vitro experiments show that CCL19 enhances the frequencies of Ag-responsive IFN-γ+CD8 + T cells from patients by approximately twofold.…”

Section: Chemokines In Hepatitis B Virus Infectionmentioning

confidence: 99%

Cytokines and Chemokines in HBV Infection

Zhong

Zhang

Tang

et al. 2021

Front. Mol. Biosci.

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Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatic inflammation and damage. The pathogenesis of chronic hepatitis B (CHB) infection is predominantly mediated by persistent intrahepatic immunopathology. With the characterization of unique anatomical and immunological structure, the liver is also deemed an immunological organ, which gives rise to massive cytokines and chemokines under pathogenesis conditions, having significant implications for the progression of HBV infection. The intrahepatic innate immune system is responsible for the formidable source of cytokines and chemokines, with the latter also derived from hepatic parenchymal cells. In addition, systemic cytokines and chemokines are disturbed along with the disease course. Since HBV is a stealth virus, persistent exposure to HBV-related antigens confers to immune exhaustion, whereby regulatory cells are recruited by intrahepatic chemokines and cytokines, including interleukin-10 and transforming growth factor β, are involved in such series of causal events. Although the considerable value of two types of available approved treatment, interferons and nucleos(t)ide analogues, effectively suppress HBV replication, neither of them is sufficient for optimal restoration of the immunological attrition state to win the battle of the functional or virological cure of CHB infection. Notably, cytokines and chemokines play a crucial role in regulating the immune response. They exert effects by directly acting on HBV or indirectly manipulating target immune cells. As such, specific cytokines and chemokines, with a potential possibility to serve as novel immunological interventions, combined with those that target the virus itself, seem to be promising prospects in curative CHB infection. Here, we systematically review the recent literature that elucidates cytokine and chemokine-mediated pathogenesis and immune exhaustion of HBV infection and their dynamics triggered by current mainstream anti-HBV therapy. The predictive value of disease progression or control and the immunotherapies target of specific major cytokines and chemokines in CHB infection will also be delineated.

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“…This is in accordance with our observation that the loss of hepatic parenchyma results in a temporary decline of CCL16 serum levels, which can be compensated by the upregulation of expression, whereas chronic liver disease, as long as sufficient functional tissue is left, does not have a significant impact. Experiments in mice indicate that the development of cirrhosis can actually be delayed by CCL16 via the inhibition of hepatic stellate cells, suggesting that this chemokine may exert a unique disease-limiting role in the liver [ 69 ]. Notably, a recent evaluation of a large number of HCC samples confirmed that mean CCL16 mRNA levels were essentially unchanged with respect to non-tumour tissue, but also revealed a low-populated tail of the distribution extending towards very high figures, which was not observed in the reference group [ 70 ].…”

Section: Resultsmentioning

confidence: 99%

Structure and Dynamics of Human Chemokine CCL16—Implications for Biological Activity

et al. 2022

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Human C-C motif ligand 16 (CCL16) is a chemokine that is distinguished by a large cleavable C-terminal extension of unknown significance. Conflicting data have been reported concerning its tissue distribution and modulation of expression, rendering the biological function of CCL16 enigmatic. Here, we report an integrated approach to the characterisation of this chemokine, including a re-assessment of its expression characteristics as well as a biophysical investigation with respect to its structure and dynamics. Our data indicate that CCL16 is chiefly synthesised by hepatocytes, without an appreciable response to mediators of inflammation, and circulates in the blood as a full-length protein. While the crystal structure of CCL16 confirms the presence of a canonical chemokine domain, molecular dynamics simulations support the view that the C-terminal extension impairs the accessibility of the glycosaminoglycan binding sites and may thus serve as an intrinsic modulator of biological activity.

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C C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

Cited by 13 publications

References 30 publications

Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease

Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease

Cytokines and Chemokines in HBV Infection

Structure and Dynamics of Human Chemokine CCL16—Implications for Biological Activity

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