{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:29:21Z","timestamp":1790497761724,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2038,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Improvements in the treatment of primary biliary cirrhosis (PBC) may depend upon dissection of mechanisms that determine recruitment of mononuclear cells to intralobular bile ducts, including the role of the chemokine-adhesion molecule CX3CL1 (fractalkine). We submit that there are unique interactions between intrahepatic biliary epithelial cells (BECs), endothelial cells (ECs), liver sinusoidal endothelial cells (LSECs), and liver-infiltrating mononuclear cells (LMCs), and that such interactions will in part dictate the biliary-specific inflammatory response. To address this, we studied fresh explanted livers from pretransplantation patients with PBC and with inflammatory liver disease due to viral infection (disease controls) and biopsy material from patients with a discrete liver tumor (normal controls). Using this clinical material, we isolated and stimulated BECs, ECs, LSECs, and LMCs with a panel of Toll-like receptor ligands. We also studied the interactions of these cell populations with LMCs with respect to adhesion capability and production of tumor necrosis factor \u03b1 (TNF-\u03b1). Finally, we used fresh biopsy samples to evaluate mononuclear cells around intrahepatic biliary ductules using monoclonal antibodies specific to CD68 or CD154, markers for monocytes\/macrophages, and activated T cells, respectively.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>There are common properties of ECs, LSECs, and BECs, whether derived from PBC or viral hepatitis, but there are also significant differences, particularly in the potential in PBC for LMCs to adhere to ECs and BECs and to produce TNF-\u03b1; such properties were associated with augmented CX3CL1 production by BEC from PBC liver. The processes defined herein suggest potential novel biotherapies for biliary specific inflammation. (Hepatology 2009.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.23318","type":"journal-article","created":{"date-parts":[[2009,11,11]],"date-time":"2009-11-11T15:02:28Z","timestamp":1257951748000},"page":"567-575","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":93,"title":["Cx3cl1 (Fractalkine): A Signpost for Biliary Inflammation in Primary Biliary Cirrhosis"],"prefix":"10.1097","volume":"51","author":[{"given":"Shinji","family":"Shimoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Niiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinobu","family":"Taketomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Maehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Tsuneyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuni","family":"Nakanuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Mackay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Gershwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Akashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-27-20241201","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1002\/hep.22102","article-title":"Biliary epithelial cells and primary biliary cirrhosis: the role of liverinfiltrating mononuclear cells.","volume":"47","author":"Shimoda","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R2-27-20241201","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0168-8278(02)00065-X","article-title":"Upregulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans.","volume":"37","author":"Efsen","year":"2002","journal-title":"J Hepatol"},{"key":"R3-27-20241201","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jhep.2007.09.008","article-title":"The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection.","volume":"48","author":"Wasmuth","year":"2008","journal-title":"J Hepatol"},{"key":"R4-27-20241201","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1172\/JCI11517","article-title":"Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses.","volume":"107","author":"Fraticelli","year":"2001","journal-title":"J Clin Invest"},{"key":"R5-27-20241201","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/art.21140","article-title":"T cell costimulation by fractalkineexpressing synoviocytes in rheumatoid arthritis.","volume":"52","author":"Sawai","year":"2005","journal-title":"Arthritis Rheum"},{"key":"R6-27-20241201","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1002\/art.22919","article-title":"Fractalkine mediates T celldependent proliferation of synovial fibroblasts in rheumatoid arthritis.","volume":"56","author":"Sawai","year":"2007","journal-title":"Arthritis Rheum"},{"key":"R7-27-20241201","doi-asserted-by":"crossref","first-page":"13173","DOI":"10.1128\/JVI.78.23.13173-13181.2004","article-title":"Human cytomegalovirusspecific CD4Tcell cytokine response induces fractalkine in endothelial cells.","volume":"78","author":"BolovanFritts","year":"2004","journal-title":"J Virol"},{"key":"R8-27-20241201","doi-asserted-by":"crossref","first-page":"949","DOI":"10.2353\/ajpath.2008.071034","article-title":"CX3CL1 upregulation is associated with recruitment of CX3CR1 mononuclear phagocytes and T lymphocytes in the lungs during cigarette smokeinduced emphysema.","volume":"173","author":"McComb","year":"2008","journal-title":"Am J Pathol"},{"key":"R9-27-20241201","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1084\/jem.20081385","article-title":"CX3CR1 CD115 CD135 common macrophageDC precursors and the role of CX3CR1 in their response to inflammation.","volume":"206","author":"Auffray","year":"2009","journal-title":"J Exp Med"},{"key":"R10-27-20241201","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/hep.20582","article-title":"Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts.","volume":"41","author":"Isse","year":"2005","journal-title":"HEPATOLOGY"},{"key":"R11-27-20241201","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1053\/j.gastro.2008.04.020","article-title":"Tolllike receptor signaling in small intestinal epithelium promotes Bcell recruitment and IgA production in lamina propria.","volume":"135","author":"Shang","year":"2008","journal-title":"Gastroenterology"},{"key":"R12-27-20241201","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/labinvest.3700453","article-title":"TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: enhanced CXCL9 in autoimmune arthritis.","volume":"86","author":"Loos","year":"2006","journal-title":"Lab Invest"},{"key":"R13-27-20241201","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1056\/NEJMra043898","article-title":"Primary biliary cirrhosis.","volume":"353","author":"Kaplan","year":"2005","journal-title":"N Engl J Med"},{"key":"R14-27-20241201","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/hep.20494","article-title":"Biliary epithelial cells regulate autoreactive T cells: implications for biliaryspecific diseases.","volume":"41","author":"Kamihira","year":"2005","journal-title":"HEPATOLOGY"},{"key":"R15-27-20241201","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1172\/JCI4213","article-title":"Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis.","volume":"102","author":"Shimoda","year":"1998","journal-title":"J Clin Invest"},{"key":"R16-27-20241201","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/S0002-9440(10)63487-6","article-title":"Capillarization of hepatic sinusoid by liver endothelial cellreactive autoantibodies in patients with cirrhosis and chronic hepatitis.","volume":"163","author":"Xu","year":"2003","journal-title":"Am J Pathol"},{"key":"R17-27-20241201","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1136\/gut.2006.093906","article-title":"Human liver sinusoidal endothelial cells induce apoptosis in activated T cells: a role in tolerance induction.","volume":"56","author":"Karrar","year":"2007","journal-title":"Gut"},{"key":"R18-27-20241201","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/hep.20434","article-title":"A novel mechanism of liver allograft rejection facilitated by antibodies to liver sinusoidal endothelial cells.","volume":"40","author":"SumitranHolgersson","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R19-27-20241201","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1016\/S0140-6736(98)05050-8","article-title":"Acquired increase in leucocyte binding by intestinal microvascular endothelium in inflammatory bowel disease.","volume":"352","author":"Binion","year":"1998","journal-title":"Lancet"},{"key":"R20-27-20241201","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1111\/j.1582-4934.2009.00787.x","article-title":"CX3Cl1fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver.","volume":"13","author":"BourdBoittin","year":"2009","journal-title":"J Cell Mol Med"},{"key":"R21-27-20241201","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1053\/j.gastro.2006.10.010","article-title":"Enhanced recruitment of CX3CR1 T cells by mucosal endothelial cellderived fractalkine in inflammatory bowel disease.","volume":"132","author":"Sans","year":"2007","journal-title":"Gastroenterology"},{"key":"R22-27-20241201","doi-asserted-by":"crossref","first-page":"5026","DOI":"10.1182\/blood-2008-06-162404","article-title":"CX3CL1fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis.","volume":"112","author":"Truman","year":"2008","journal-title":"Blood"},{"key":"R23-27-20241201","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1084\/jem.20041035","article-title":"Hepatic endothelial CCL25 mediates the recruitment of CCR9 guthoming lymphocytes to the liver in primary sclerosing cholangitis.","volume":"200","author":"Eksteen","year":"2004","journal-title":"J Exp Med"},{"key":"R24-27-20241201","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/bjp.2008.180","article-title":"The selective MMP12 inhibitor, AS111793 reduces airway inflammation in mice exposed to cigarette smoke.","volume":"154","author":"Le Quement","year":"2008","journal-title":"Br J Pharmacol"},{"key":"R25-27-20241201","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/82161","article-title":"Efficient presentation of exogenous antigen by liver endothelial cells to CD8 T cells results in antigenspecific Tcell tolerance.","volume":"6","author":"Limmer","year":"2000","journal-title":"Nat Med"},{"key":"R26-27-20241201","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1002\/hep.22763","article-title":"Chemokines in the immunopathogenesis of hepatitis C infection.","volume":"49","author":"Heydtmann","year":"2009","journal-title":"HEPATOLOGY"},{"key":"R27-27-20241201","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/hep.22011","article-title":"Coculture of human liver macrophages and cholangiocytes leads to CD40dependent apoptosis and cytokine secretion.","volume":"47","author":"Alabraba","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R28-27-20241201","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1096\/fj.01-0088com","article-title":"CD40 activationinduced, Fasdependent apoptosis and NFkappaBAP1 signaling in human intrahepatic biliary epithelial cells.","volume":"15","author":"Afford","year":"2001","journal-title":"FASEB J"},{"key":"R29-27-20241201","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/hep.22591","article-title":"Differential mechanisms in the pathogenesis of autoimmune cholangitis versus inflammatory bowel disease in interleukin2Ralpha() mice.","volume":"49","author":"Hsu","year":"2009","journal-title":"HEPATOLOGY"},{"key":"R30-27-20241201","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.4049\/jimmunol.177.3.1655","article-title":"Antimitochondrial antibodies and primary biliary cirrhosis in TGFbeta receptor II dominantnegative mice.","volume":"177","author":"Oertelt","year":"2006","journal-title":"J Immunol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.23318","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201002000-00027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T13:30:27Z","timestamp":1733059827000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201002000-00027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.23318","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2010,2]]}}}