Biliary Epithelial Cells Are Not the Predominant Source of Hepatic CXCL12.
Biliary Epithelial Cells Are Not the Predominant Source of Hepatic CXCL12.
复制标题
DOI：
10.1016/j.ajpath.2015.03.006
复制
发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Yedidya Saiman;Tatsuki Sugiyama;Noa Simchoni;C. Spirli;M. Bansal
中科院分区：
文献类型：
--
作者：
Yedidya Saiman;Tatsuki Sugiyama;Noa Simchoni;C. Spirli;M. Bansal
在所有形式的肝损伤期间，CXCL 12（在炎症和干细胞募集中重要的趋化因子）及其受体C-X-C趋化因子受体4的肝表达水平增加。CXCL 12由实质和非实质肝细胞表达，并且基于免疫组织化学，胆管上皮细胞（BEC）被认为是肝CXCL 12的主要来源，从而促进C-X-C趋化因子受体4表达淋巴细胞的门脉周募集。我们的研究旨在表明，BEC可能，事实上，不是肝脏CXCL 12的主要来源。我们使用酶联免疫吸附测定和Western印迹分析分别从细胞培养上清液和全细胞裂解物测量来自人和鼠BEC的CXCL 12分泌和表达，而在aCxcl 12-Gfpreporter小鼠中分析鼠肝脏中的CXCL 12表达。来自BEC的细胞培养上清液和全细胞裂解物未能证明其CXCL 12的表达。此外，我们用aCxcl 12-Gf前转运体小鼠证实了这些结果，其中绿色荧光蛋白表达在BEC中明显缺失。有趣的是，在绿色荧光蛋白表达的基础上，我们证明了一个群体的CXCL 12表达细胞内的门静脉束是不同的，但密切相关的BEC。这些发现表明BEC不是CXCL 12的主要来源。
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 aCxcl12-Gfpreporter mouse. Cell culture supernatants and whole cell lysates from BECs failed to demonstrate their expression of CXCL12. Furthermore, we confirmed these results with aCxcl12-Gfpreporter 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.