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The chemokine CCL21 modulates lymphocyte recruitment and fibrosis in chronic hepatitis C.
- Source :
-
Gastroenterology [Gastroenterology] 2003 Oct; Vol. 125 (4), pp. 1060-76. - Publication Year :
- 2003
-
Abstract
- Background and Aims: The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation. We investigated the expression of CCL21 and CCR7 in chronic hepatitis C. The effects of CCL21 on hepatic stellate cells (HSCs) were also studied.<br />Methods: Expression of CCL21 was assessed by in situ hybridization and immunohistochemistry. CCR7 on T cells was analyzed by flow cytometry. Cultured human HSCs were studied in their activated phenotype.<br />Results: In patients with chronic hepatitis C, expression of CCL21 and CCR7 was up-regulated. CCL21 was detected in the portal tracts and around inflammatory lymphoid follicles, in proximity to T lymphocytes and dendritic cells, which contributed to expression of this chemokine. Expression of CCR7 was also increased in patients with primary biliary cirrhosis. Intrahepatic CD8(+) T lymphocytes isolated from patients with chronic hepatitis C had a significantly higher percentage of positivity for CCR7 than those from healthy controls, and the expression of CCR7 was associated with that of CXCR3. Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model. Exposure of HSCs to CCL21 triggered several signaling pathways, including extracellular signal-regulated kinase, Akt, and nuclear factor kappaB, resulting in induction of proinflammatory genes.<br />Conclusions: Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs.
- Subjects :
- Cell Movement drug effects
Cell Nucleus immunology
Cell Nucleus metabolism
Cells, Cultured
Chemokine CCL21
Chemokines, CC genetics
Chemokines, CC pharmacology
Gene Expression immunology
Hepatitis C, Chronic pathology
Hepatitis C, Chronic physiopathology
Humans
Liver cytology
Liver Cirrhosis pathology
Liver Cirrhosis virology
Lymphoid Tissue immunology
Lymphoid Tissue pathology
MAP Kinase Kinase 2
MAP Kinase Signaling System immunology
Mitogen-Activated Protein Kinase Kinases metabolism
Mitogen-Activated Protein Kinases metabolism
NF-kappa B metabolism
Protein Serine-Threonine Kinases metabolism
Protein-Tyrosine Kinases metabolism
Receptors, CCR7
Receptors, Chemokine genetics
Receptors, Chemokine metabolism
Recombinant Proteins pharmacology
T-Lymphocytes physiology
Cell Movement immunology
Chemokines, CC metabolism
Hepatitis C, Chronic immunology
Liver Cirrhosis immunology
MAP Kinase Kinase Kinase 1
T-Lymphocytes pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0016-5085
- Volume :
- 125
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 14517790
- Full Text :
- https://doi.org/10.1016/s0016-5085(03)01194-6