Biliary Epithelial Cells Are Not the Predominant Source of Hepatic CXCL12.
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.
Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Yedidya
Y
Saiman
Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Tatsuki
T
Sugiyama
Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Noa
N
Simchoni
Liver Center and Digestive Diseases Section, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
Carlo
C
Spirli
Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: meena.bansal@mssm.edu.
Meena B
MB
Bansal
D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D011993:Recombinant Fusion Proteins