Fractalkine and CX3CR1 are involved in the recruitment of Intraepithelial lymphocytes of intrahepatic bile ducts
Fractalkine and CX3CR1 are involved in the recruitment of Intraepithelial lymphocytes of intrahepatic bile ducts
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DOI：
10.1002/hep.20582
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发表时间：
2005-03-01
期刊：
影响因子：
13.5
通讯作者：
Nakanuma, Y
中科院分区：
文献类型：
--
作者：
Isse, K;Harada, K;Nakanuma, Y
Fractalkine是一种具有趋化因子和细胞粘附功能的趋化因子，在肠道中，它与其受体CX 3CR 1一起参与上皮内淋巴细胞的趋化和募集。我们研究了fractalkine和CX 3CR 1在正常和病变胆管中的病理生理作用。检测17例原发性胆汁性肝硬化患者和9例原发性硬化性胆管炎、10例肝外胆管梗阻、20例慢性丙型肝炎和18例正常肝组织中Fractalkine和CX 3CR 1的表达。使用人胆管癌细胞系（HuCC-T1）和人肝内BEC系检查了响应细胞因子处理的胆汁上皮细胞（BEC）中fractalkine的表达。使用趋化室测定表达CX 3CR 1的单核细胞（THP-1）对fractalkine的趋化性。Fractalkine信使RNA/蛋白在正常和病变胆管的BEC上表达，并且其在原发性胆汁性肝硬化损伤胆管中的表达上调。CX 3CR 1在原发性胆汁性肝硬化汇管区浸润的单个核细胞和损伤胆管的CD 3（+）、CD 4（+）和CD 8（+）上皮内淋巴细胞上表达。Fractalkine信使RNA表达上调两个培养的BEC治疗与脂多糖和Th 1细胞因子（白细胞介素1 β，干扰素γ，和肿瘤坏死因子α）。THP-1细胞对培养细胞分泌的Fractalkine具有趋化性。总之，原发性胆汁性肝硬化导致的受损胆管微环境中的Th 1细胞因子优势和脂多糖诱导BEC中fractalkine表达上调，随后是表达CX 3CR 1的单核细胞（包括CD 4（+）和CD 8（+）T细胞）的化学吸引，以及它们与BEC的粘附和胆汁上皮内淋巴细胞的积累。
Fractalkine is a chemokine with both chemoattractant and cell-adhesive functions, and in the intestine it is involved with its receptor CX3CR1 in the chemoattraction and recruitment of intraepithelial lymphocytes. We examined the pathophysiological roles of fractalkine and CX3CR1 in normal and diseased bile ducts. Expression of fractalkine and CX3CR1 were examined in liver tissues from patients with primary biliary cirrhosis (17 cases) and controls (9 cases of primary sclerosing cholangitis, 10 cases of extrahepatic biliary obstruction, 20 cases of chronic viral hepatitis C, and 18 cases of histologically normal livers). Expression of fractalkine in biliary epithelial cells (BECs) in response to cytokine treatments was examined using a human cholangiocarcinoma cell line (HuCC-T1) and human intrahepatic BEC line. The chemotaxis of CX3CR1-expressing monocytes (THP-1) toward fractalkine was assayed using chemotaxis chambers. Fractalkine messenger RNA/protein were expressed on BECs of normal and diseased bile ducts, and their expression was upregulated in injured bile ducts of primary biliary cirrhosis. CX3CR1 was expressed on infiltrating mononuclear cells in portal tracts and on CD3(+), CD4(+), and CD8(+) intraepithelial lymphocytes of injured bile ducts in primary biliary cirrhosis. Fractalkine messenger RNA expression was upregulated in two cultured BECs on treatment with lipopolysaccharide and Th1-cytokines (interleukin 1beta, interferon gamma, and tumor necrosis factor alpha). THP-1 cells showed chemotaxis toward fractalkine secreted by cultured cells. In conclusion, Th1-cytokine predominance and lipopolysaccharide in the microenvironment of injured bile ducts resulting from primary biliary cirrhosis induce the upregulation of fractalkine expression in BECs, followed by the chemoattraction of CX3CR1-expressing mononuclear cells, including CD4(+) and CD8(+) T cells, and their adhesion to BECs and the accumulation of biliary intraepithelial lymphocytes.