Biliary Epithelial Cells Are Not the Predominant Source of Hepatic CXCL12

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 4eexpressing 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. (Am J Pathol 2015 http://dx

A Novel Tissue‐Based Liver–Kidney‐on‐a‐Chip Can Mimic Liver Tropism of Extracellular Vesicles Derived from Breast Cancer Cells

“…Reconstitution of the chemokine microenvironment of each organ is difficult by culturing single cell types in vitro because chemokines are secreted by variety of cell types. CXCL12 is produced by both parenchymal and nonparenchymal hepatic cells in the liver . Thus, tissue culture is a better choice to reconstitute the chemokine microenvironment of an organ.…”

“…CXCL12 is produced by both parenchymal and nonparenchymal hepatic cells in the liver. [46][47][48][49] Thus, tissue culture is a better choice to reconstitute the chemokine microenvironment of an organ. Cell culture-based liver-on-a-chip and kidney-on-a-chip have been reported previously.…”

The Influence of Chronic Liver Diseases on Hepatic Vasculature: A Liver-on-a-chip Review

“…In addition to hepatocytes, stellate, Kupffer, and endothelial cells, bile duct cells and other immune cells such as T-cells, play roles in different disease states in liver. Bile duct cells (cholangiocytes) are the epithelial cells surrounding the bile duct and are responsible for the modification of hepatocyte-derived bile processes regulated by hormones, peptides, nucleotides, neurotransmitters, and other molecules along with intracellular signaling pathways and cascades [77]. Currently, two immortalized cholangiocyte cell lines (H69 and NHC) have been used in in vitro studies [78].…”