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Am J Pathol. 2015 Jul;185(7):1859-66. doi: 10.1016/j.ajpath.2015.03.006. Epub 2015 Apr 29.

Biliary Epithelial Cells Are Not the Predominant Source of Hepatic CXCL12.

Author information

1
Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
2
Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
3
Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
4
Liver Center and Digestive Diseases Section, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
5
Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: meena.bansal@mssm.edu.

Abstract

Hepatic expression levels of CXCL12, a chemokine important in inflammatory and stem cell recruitment, and its receptor, C-X-C chemokine receptor 4, are increased during all forms of liver injury. CXCL12 is expressed by both parenchymal and nonparenchymal hepatic cells, and on the basis of immunohistochemistry, biliary epithelial cells (BECs) are thought to be a predominant source of hepatic CXCL12, thereby promoting periportal recruitment of C-X-C chemokine receptor 4-expressing lymphocytes. Our study aims to show that BECs may, in fact, not be the predominant source of hepatic CXCL12. We measured CXCL12 secretion and expression from human and murine BECs using enzyme-linked immunosorbent assay and Western blot analysis from cell culture supernatants and whole cell lysates, respectively, whereas CXCL12 expression in murine livers was analyzed in a Cxcl12-Gfp reporter mouse. Cell culture supernatants and whole cell lysates from BECs failed to demonstrate their expression of CXCL12. Furthermore, we confirmed these results with a Cxcl12-Gfp reporter mouse in which green fluorescent protein expression is notably absent from BECs. Interestingly, on the basis of green fluorescent protein expression, we demonstrate a population of CXCL12-expressing cells within the portal tract that are distinct, yet intimately associated with BECs. These findings indicate that BECs are not a predominant source of CXCL12.

PMID:
25934614
PMCID:
PMC4483462
DOI:
10.1016/j.ajpath.2015.03.006
[Indexed for MEDLINE]
Free PMC Article
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