Stromal cell-derived factor-1 from biliary epithelial cells recruits CXCR4-positive cells: Implications for inflammatory liver diseases

Ryo Terada, Kazuhide Yamamoto, Tomomi Hakoda, Noriaki Shimada, Nobuaki Okano, Nobuyuki Baba, Yoshifumi Ninomiya, M. Eric Gershwin, Yasushi Shiratori

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85 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)665-672
Number of pages8
JournalLaboratory Investigation
Volume83
Issue number5
StatePublished - May 1 2003

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Terada, R., Yamamoto, K., Hakoda, T., Shimada, N., Okano, N., Baba, N., Ninomiya, Y., Gershwin, M. E., & Shiratori, Y. (2003). Stromal cell-derived factor-1 from biliary epithelial cells recruits CXCR4-positive cells: Implications for inflammatory liver diseases. Laboratory Investigation, 83(5), 665-672.