Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans

Efsen, Eva; Grappone, Cecilia; DeFranco, Raffaella; Milani, Stefano; Romanelli, Roberto Giulio; Bonacchi, Andrea; Caligiuri, Alessandra; Failli, Paola; Annunziato, Francesco; Pagliai, Gabriella; Pinzani, Massimo; Geñtilini, Paolo; Marra, Fabio

doi:10.1016/s0168-8278(02)00065-x

Cited by 97 publications

(83 citation statements)

References 35 publications

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“…This pattern of expression mirrors that found in epithelial cells of biliary ductules (44) but differs markedly from that of intestinal epithelial cells, where CX 3 CL1 largely is expressed in the basolateral membrane and in regions of intercellular contact (45,46). In the intestine, as in the kidney, expression of CX 3 CL1 is highly enhanced in disease states that are marked by active inflammation (14,45,47).…”

Section: Discussionsupporting

confidence: 70%

“…In contrast, no such immunosurveillance is known to occur within the kidney or the intrahepatic biliary tree. In biliary ductular epithelial cells, CX 3 CL1 is expressed both apically and basolaterally (44,47). CX 3 CL1 on the apical surface of regenerating biliary epithelial cells has been implicated in repair of the biliary tree after acute injury, presumably by recruiting hepatic stem cells, which express CX 3 CR1 (47).…”

Section: Discussionmentioning

confidence: 99%

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Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Durkan¹,

Alexander²,

Liu³

et al. 2007

Journal of the American Society of Nephrology

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The chemokine CX 3 CL1 plays a key role in glomerulonephritis and can act as both chemoattractant and adhesion molecule. CX 3 CL1 also is upregulated in tubulointerstitial injury, but little is known about the subcellular distribution and function of CX 3 CL1 in renal tubular epithelial cells (RTEC). Unexpectedly, it was found that CX 3 CL1 is expressed predominantly on the apical surface of tubular epithelium in human renal transplant biopsy specimens with acute rejection or acute tubular necrosis. For studying the targeting of CX 3 CL1 in polarized RTEC, MDCK cells that expressed untagged or green fluorescent protein-tagged CX 3 CL1 were generated. The chemokine was present on the apical membrane and in subapical vesicles. Apical targeting of CX 3 CL1 was not due to signals that were conferred by its intracellular domain, to associations with lipid rafts, or to O-glycosylation but, rather, depended on N-linked glycosylation of the protein. With the use of fluorescence recovery after photobleaching, it was found that CX 3 CL1 is immobile in the apical membrane. However, CX 3 CL1 partitioned with the triton-soluble rather than -insoluble cellular fraction, indicating that it is not associated directly with the actin cytoskeleton or with lipid rafts. Accordingly, disruption of rafts through cholesterol depletion did not render CX 3 CL1 mobile. For exploration of potential functions of apical CX 3 CL1, binding of CX 3 CR1-expressing leukocytes to polarized RTEC was examined. Leukocyte adhesion to the luminal surface was enhanced significantly when CX 3 CL1 was present. These data demonstrate that CX 3 CL1 is expressed preferentially on the apical membrane of RTEC and suggest a novel function for the chemokine in recruitment and retention of leukocytes in tubulointerstitial inflammation.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Durkan¹,

Alexander²,

Liu³

et al. 2007

Journal of the American Society of Nephrology

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“…10,11 For ex-ample, Terada et al 12 reported that stromal-derived factor 1 expressed on bile ducts is responsible for the migration and recruitment of lymphoid cells in portal tracts and around bile ducts in primary biliary cirrhosis (PBC) as well as in chronic viral hepatitis (CVH). Although the upregulation of fractalkine and CX3CR1 expression has been reported in hepatic parenchyma and bile ductules of hepatitis C virus-infected livers, 13 their expression and immunopathological significance remain unexplored in normal and pathological bile ducts.…”

mentioning

confidence: 99%

Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts†

et al. 2005

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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

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“…Efsen et al observed that both fractalkine and CX3CR1 are up-regulated during chronic injury, in areas of portal and lobular inflammation (14). In severe acute hepatitis, fractalkine and CX3CR1 are expressed at high levels both at in areas of inflammation and in regenerating epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…The membrane-anchored form of fractalkine consists of a chemokine head tethered to the cell surface by a mucin-like stalk, followed by a single trans-membranespanning domain. Fractalkine is expressed on endothelial cells, dendritic cells, and intestinal epithelial cells (12)(13)(14). CX3CR1, the unique receptor of fractalkine, belongs to a family of specific G protein-coupled seven-transmem-brane domain receptors, and is expressed on T cells, natural killer cells, monocytes, and microvascular endothelial cells (15).…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of fractalkine inhibits the in vitro and in vivo angiogenesis of the hepatocellular carcinoma HepG2 cells

Wang¹

2010

Oncol Rep

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Abstract. There is increasing evidence that hepatocellular carcinoma (HCC) is inherently associated with the inflammatory process and the up-regulation of cytokines. Our study aimed at elucidating the role of the cytokine fractalkine in the process of HCC carcinogenesis. Expression of fractalkine in hepatocellular carcinoma cell line HepG2 was knocked-down by RNAi. Conditioned media (CMs) from HepG2 was used in angiogenesis assays both in vitro and in vivo. Compared with CMs from mock transfection and negative shRNA treated HepG2, CMs from fractalkine shRNA treated HepG2 highly suppressed the migration, proliferation, and differentiation of human umbilical vein endothelial cells. The results suggest that fractalkine may play a key role in the mechanism of angiogenesis and carcinogenesis of HCC.

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Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans

Cited by 97 publications

References 35 publications

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts†

Down-regulation of fractalkine inhibits the in vitro and in vivo angiogenesis of the hepatocellular carcinoma HepG2 cells

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