Related Experiment Videos
Stromal cell-derived factor-1 from biliary epithelial cells recruits CXCR4-positive cells: implications for
Ryo Terada1, Kazuhide Yamamoto, Tomomi Hakoda
1Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Insights
Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are upregulated in inflammatory liver diseases. Increased SDF-1 from biliary epithelial cells attracts CXCR4-positive inflammatory cells, suggesting therapeutic potential.
Area of Science:
- Hepatology
- Immunology
- Cell Biology
Background:
- Stromal cell-derived factor-1 (SDF-1) is crucial for fetal liver hematopoiesis, but its postnatal role is unclear.
- Inflammatory liver diseases involve complex cellular interactions and immune responses.
Purpose of the Study:
- To investigate the role of SDF-1 and its receptor CXCR4 in various inflammatory liver diseases.
- To determine the cellular source and expression levels of SDF-1 and CXCR4 in diseased liver tissue and plasma.
Main Methods:
- Analysis of 75 patients with liver diseases (viral hepatitis, cirrhosis, etc.) and controls.
- RT-PCR and laser capture microdissection for single-cell SDF-1 expression in biliary epithelial cells (BEC).
- Flow cytometry to assess CXCR4 expression on liver-infiltrating lymphocytes (LILs) and peripheral blood lymphocytes (PBLs).
Main Results:
- SDF-1 was upregulated in BEC of interlobular and septal bile ducts and proliferated bile ductules in inflammatory liver diseases.
- Plasma SDF-1 levels were significantly higher in patients with liver diseases compared to controls.
- Most LILs expressed CXCR4, with significantly higher intensity on LILs than PBLs.
Conclusions:
- Increased SDF-1 production by BEC contributes to the recruitment of CXCR4-positive inflammatory cells into diseased livers.
- The SDF-1/CXCR4 axis represents a potential therapeutic target for inflammatory liver diseases.
Abstract:
Although stromal cell-derived factor-1 (SDF-1) plays an important role in hematopoiesis in the fetal liver, the role after birth remains to be clarified. We investigated the role of SDF-1 and its receptor, CXCR4, in 75 patients; this included controls and patients with viral hepatitis, liver cirrhosis, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Interestingly, SDF-1 appeared up-regulated in biliary epithelial cells (BEC) of inflammatory liver disease. Furthermore, in inflammatory liver diseases, SDF-1 was expressed by BEC of interlobular and septal bile ducts and by proliferated bile ductules. The message expression of SDF-1 in BEC was confirmed at a single-cell level by RT-PCR and laser capture microdissection. The plasma levels of SDF-1 were significantly higher in patients with liver diseases than in normal controls. Flow cytometric analysis of the surface expression of CXCR4 showed that most liver-infiltrating lymphocytes express CXCR4 and the intensity was up-regulated more significantly in liver-infiltrating lymphocytes than in peripheral blood lymphocytes. These results suggest that increased SDF-1 production by BEC may play an important role in the recruitment of CXCR4-positive inflammatory cells into the diseased livers. These data are significant because modulation of the SDF-1/CXCR4 interaction has therapeutic implications for inflammatory liver diseases.