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CCL20 (CC chemokine ligand 20) is emerging as an important regulatory molecule in a pathway common to virus infection, alcoholic hepatitis, and non-alcoholic fatty liver disease (NAFLD) leading to the development of hepatic fibrosis. We previously observed upregulation of CCL20 in patients with NAFLD fibrosis and human hepatic stellate cells (LX-2 cells) in response to lipid loading. To date, the mechanisms mediating the relationship between CCL20 and hepatic fibrogenesis remain unknown. In this study, we sought to characterize the molecular mechanisms by which CCL20 may contribute to fibrogenesis in NAFLD. We observed that CCL20 levels increased with worsening severity of liver histology in NAFLD patients (normal < steatosis < inflammation < fibrosis) and during LX-2 cell activation in a time-dependent manner. We found that treatment of LX-2 cells with CCL20 corresponded with increased levels of CCL20 and ACTA2, and decreased levels of PLAU and SERPINE1, effects mitigated by CCL20 knockdown. We identified a putative binding site for miR-590-5p, which we previously reported to be downregulated in NAFLD fibrosis, in the CCL20 3' untranslated region (3'UTR), and found that exogenous miR-590-5p functionally interacted with the CCL20 3'UTR to downregulate its expression. Transfection of LX-2 hepatic stellate cells with miR-590-5p mimic or silencing RNA resulted in decreased or increased CCL20 levels, respectively. Our results indicate an association between CCL20 and hepatic stellate cell activation that includes modulation of key ECM components and functional interactions with a miRNA previously implicated in NAFLD fibrosis. Together, these findings support a novel mechanism by which CCL20 may promote fibrogenesis in NAFLD.
This article was published in the following journal.
The ligand/receptor pair C‑C motif chemokine ligand 20 (CCL20)/C‑C motif chemokine receptor 6 (CCR6) is considered to be highly activated in lung cancer and significantly accelerates lung cancer p...
Chronic rhinosinusitis (CRS) is a local inflammation of the nasal mucosa and sinus that persists for >12 weeks. As CC chemokine ligand (CCL) 19 expression is known to be elevated in CRS, and CCL 19, C...
Endometriosis is a chronic inflammatory disease which is associated with aberrant chemokine expression. We have established a three-dimensional (3D) floating collagen gel culture of human endometrioti...
CCL20, as a chemokine, plays an important role in rheumatoid arthritis, psoriasis, and other diseases by binding to its receptor CCR6. Recent 10 years' research has demonstrated that CCL20 also contri...
Mucosal wound repair is coordinated by dynamic crosstalk between endogenous and exogenous mediators and specific receptors on epithelial cells and infiltrating immune cells. One class of such receptor...
Chemokine (C-C motif) ligand 20 (CCL20) is a protein involved in attracting immune cells including subsets of T cells (for example Th17 cells), B cells, natural killer cells and dendritic ...
It's a single arm, open label prospective study, in which the safety and efficacy of Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T therapy are evaluated in refrac...
Systemic lupus erythematosus (SLE) is systemic autoimmune disease characterized by various immunological abnormalities, including dysregulated activation of both T and B lymphocytes with o...
This study aims to elucidate the role of Chemokine and chemokine receptor in the pathogenesis of Psoriasis by using human psoriasis skin xenograft SCID mouse model. The hypothesis is that ...
Non-alcoholic fatty liver diseases (NAFLD) include several entities ranging from simple steatosis to hepatic fibrosis or cirrhosis. Steatosis, considered benign and the first stage of the ...
A CC-type chemokine with specificity for CCR6 RECEPTORS. It has activity towards DENDRITIC CELLS; T-LYMPHOCYTES; and B-LYMPHOCYTES.
CCR receptors with specificity for CHEMOKINE CCL20. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS.
A CC chemokine with specificity for CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES and a variety of other immune cells. This chemokine is encoded by multiple genes.
A CC chemokine with specificity for CCR1 RECEPTORS and CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES; and a variety of other immune cells. This chemokine is encoded by multiple genes.
CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.
Cytokines include chemokines, lymphokines, and monokines. Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to...
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...